dr.nur anissah ans-uii 2okt'09 komunikasi seluler&konsep reseptor
Post on 10-Feb-2018
220 Views
Preview:
TRANSCRIPT
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
1/82
Komunikasi seluler dan
Konsep reseptor
Nur Anisah
Bagian Histologi&BiologiSel
Facultas Kedokteran
Universitas Gadjah Mada
11/25/2013 nur anisah 1
http://en.wikipedia.org/wiki/File:Community_of_Cells.jpg -
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
2/82
11/25/2013 nur anisah 2
SEL
Berkomunikasi : * Hidup
* Berfungsi baik
* Berproliferasi
Jika tidak mendapat rangsangan yang diperlukan
mengaktifkan program untuk membunuhdirinya sendiri
Sel dapat berkomunikasi dengan sel lainnya secara:
* kontak fisik
* molekul sekresi
* hubungan sitoplasma (gap junctions)
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
3/82
Komunikasi interseluler :
MOLEKUL SINYAL : * Asam amino
* Polipeptida* Steroid
* Mikromolekul
Misal: - Hormon
- Sitokin
- Growth factor- Neurotransmitter
11/25/2013 nur anisah 3
Molekul sinyal
Fungsi : Sebagai ligan: akan mengubah konfigurasi
protein penyusun reseptor yg diikatnya
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
4/82
11/25/2013 nur anisah 4
Pesan dari sel lain :
Memproduksi suatu protein tertentu
Mengeluarkan suatu produk ke luar sel
Merubah bentuk sel
Supaya sel berpindah ke tempat lain
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
5/82
11/25/2013 nur anisah 5
TIPE KOMUNIKASI ANTAR-SEL:
1. KOMUNIKASI LANGSUNG (Direct
Communication) Junctional
complexes / gap junctions
2. KOMUNIKASI TIDAK LANGSUNG (Indirect
Communication) Menggunakanbeberapa macam molekul sinyal
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
6/82
Epithelial cells communicate and adhere
to each other and/or to the underlyingbasement membrane by diverse junctions.
11/25/2013 nur anisah 6
Specialized junctions provide attachmentand mechanical strength to the epithelialcells, and mediate signals from the
neighboring cells or from the extracellularmatrix to the cytoskeleton and the corticalcell cytoplasm.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
7/82
11/25/2013 nur anisah 7
Finally, synaptic signaling is found in the nervous system. It is a highly specific and localized type of
paracrine signalling between two nerve cells or between a nerve cell and a muscle cell. We will go into
details of synaptic signaling when we cover the human nervous system.
Epithelial cells communicate and adhere to each
other and/or to the underlying basement
membrane by diverse junctions.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
8/82
11/25/2013 nur anisah 8
Figure Schematic
representation of cell junctions
in simple epithelium.
Specialized junctions
- provide attachment
- mechanical strengthto the epithelial
cells
- mediate signals
* from the
neighboring cells
* or from the
extracellular matrix
to the cytoskeleton
and the cortical cell
cytoplasm.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
9/82
11/25/2013 nur anisah 9
HUBUNGAN ANTAR-SEL
Bangunan khusus pada permukaan sel
Apical
Lateral
Basal
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
10/82
11/25/2013 nur anisah 10
There are two major ways in which cells in tissues can
be held together;:
1. An extracellular matrix of macromolecules can
form a lattice-work that can then be used by
the associated cells to move, change positionand a framework in which cells can interact
with one another,
2. Cell junctionscan create firm, direct, specialized
points of fusion between two cells in directphysical contact.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
11/82
11/25/2013 nur anisah 11
SummaryTable of Animal Cell-Cell Junctions:
Name of
JunctionImportant Structural Features Function
Gap
Junction
Connexons; small gap between cells (2-4
nm)
Passage of small molecules and
ions (signaling & nutrition)
Tight
Junction
Fusion of ridges of membrane -- no gap at
ridge.
Water Tight Seal between cells;
divide membrane into regions
Adhesive
or
Anchoring
Junctions
Intracellular Plaques with filaments.
Classified by:
(a) Shape of plaque: spot vs belt
(b) Type of filaments:
IF (desmosomes) vs MF (adherensjunctions)
Cell/cell protein connectors = cadherins
Larger gap between cells (25-35 nm)
Strength
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
12/82
Tight junctions
In the simple epithelia, the tight junctions form apermeability barrier and divide the plasma
membrane of the cell to the basolateral andapical domains.
Are linked to microfilaments, and they compriseof transmembrane proteins (occludin andclaudin), and the cytoplasmic plaque molecules.
Have not been characterized in human skin. However, the tight junctional antigens and
structural elements have been shown to locatein the granular layer of skin.
11/25/2013 nur anisah 12
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
13/82
11/25/2013 nur anisah 13
Many surfaces of an animal
body, and many linings insidean animal's body,
consist of sheets of cells that
act as highly selective
barriers to the passage
of materials, in eitherdirection. These cell sheets
separate the two sides of
the organ or structure (the
"inside" and the "outside"),
and usually these two
"sides" have very different
chemical compositions, that
must be kept separate
and apart.
Tight Junctions
Barriers across sheets of cells
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
14/82
11/25/2013 nur anisah 14
For example, the epithelial cells that line the small intestine
in humans are arranged into a sheet of cells that separate
the contents of the guts and the inner cavity of the organ
that eventually empties into blood vessels.
Special tight junctions between the cells of the
epithelium are very important in helping the cells
stay together as a sheet of cells (i.e. joining them
to one another) and also helping the cells act as a
very selective barrier.
While acting as a barrier that prevents the semi-digested
food from mixing into the bodily fluids, this sheet of
epithelial cells must also act as a very selective pump,pumping required nutrients (such as glucose) from the
digesting food and into the blood.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
15/82
11/25/2013 nur anisah 15
Gap Junctions
Gap junctions are more accurately considered to be
communicating junctions rather than cell adhesion
junctions.But their structure likely results in both functions. Gap
junctions are known to appear at specific
times to mediate certain events.
For example, gap junctions appear in the myometrium
of the uterus during the later stages of pregnancy so
that the uterine contractions can be precisely
controlled during childbirth.
During development, gap junctions appear in
developing muscle cells (myoblasts) to co-ordinatetheir fusion into future muscle fibres (myoblasts).
These topics are covered in the lecture on
biomembrane fusion.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
16/82
11/25/2013 nur anisah 16
Gap Junction Structure
The following shows how gap junctions appear in the transmission and
scanning electron microscopes. The third picture shows what purified gap
junctional components look like.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
17/82
11/25/2013 nur anisah 17
Gap Junctions
Passage of small molecules
- Gap junctions are probably the
most common type of join
between two cells,
and are found in almost all animal
tissues.
- Each junction allows small,
water soluble molecules to move
directly between the cytoplasms
of the two cells in contact, whichmeans that both cells share
metabolites and even electrical
properties.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
18/82
11/25/2013 nur anisah 18
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
19/82
11/25/2013 nur anisah 19
The gap junction will be discussed in more detail in the lecture on cell
communication.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
20/82
11/25/2013 nur anisah 20
Penetrability determined by EM and microinjection studies (e.g.,
flourescent dyes, labelled molecules, etc.)
Molecules greater than 5000 MW cannot pass
Molecules less than 5000 MW can pass
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
21/82
11/25/2013 nur anisah 21
As will become clear when we discuss the roles of calcium ions,
cyclic AMP and IP3, the ability of small molecules to transfer
between cells via gap junctions has important implications to cell
function.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
22/82
Desmosomes
are cell-cell junctions, which are attached to the
intermediate filaments
mediate a strong adhesion between the epidermal
keratinocytes from the basal to the cornified layer
These junctions can rapidly respond to environmental
changes, and allow the dynamic processes such as
wound healing to occur
The molecules forming the transmembrane calcium-
dependent part of the demosome are desmocollins
(types 1-3) and desmogleins (types 1-3).
The cytoplasmic plaque contains plakoglobin, and
desmoplakins (type 1-3).
11/25/2013 nur anisah 22
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
23/82
11/25/2013 nur anisah 23
Basal membrane
Hemidesmosomes are the cell-matrix junctions, which mediate adhesion between
the basal cells and the basement membrane- The cytoplasmic plaque is composed of plectin and BPAG1
(BP230), which are linked to intermediate filaments.
- The molecules of a transmembrane part of the junction
are the integrin 6 4, and BPAG2 (BP180/collagen XVII)
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
24/82
Adherens junctions Mediate the cell-cell contacts of all living cell layers of
the epidermis.
These junctions are connected to microfilamentous
cytoskeleton.
The transmembrane molecules of the adherens junction
are the calcium-dependent E- or P-cadherins, while the
plaque consists of plakoglobin and - and -catenin .
The assembly of adherens junctions seems to be a
driving force for the formation of other cell junctions
(e.g. desmosomes) .
In addition to their adhesive function in epidermis, the
adherens junctions have been assumed to participate in
cellular communication, migration, and tissue
morphogenesis.
11/25/2013 nur anisah 24
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
25/82
Focal adhesions
have been shown to appear in keratinocytes in vitro, andthese molecules may play a role in e.g. the migration of thecells during wound healing .
mediate the cell-matrix interactions (such as betweenkeratinocytes and the cell culture substratum) and arelinked to the microfilaments.
The molecular structure of the focal adhesions comprise atransmembrane 2/3 1-integrins, and the cytoplasmicplaque containing vinculin, talin, -actinin, and paxillin.
Recent evidence has suggested that syndecan-4transmembrane proteoglycan, might control the assemblyof the focal adhesions.
11/25/2013 nur anisah 25
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
26/82
11/25/2013 nur anisah 26
Cell Adhesion molecules
Family Ligands recognaized Stable cell
Junction Selection carbohydrat No
Integrins Extracellular matrix
Member of Ig
superfamily
Ig superfamily
No
Focal adhesions and
hemidesmosomes
No
Integrins Homophilic interaction No
Cadherins Homophilic interaction Focal adhesions and
hemidesmosomes
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
27/82
11/25/2013 nur anisah 27
Cell Fusion
Cell fusion (e.g., sperm and egg) might be
considered as a type of cellular communicationsince it involves the total sharing of cytoplasmic
constituents. During fertilization, nuclear fusion
also results in the intermingling of haploid
genomes, generating a new diploid genome.
Cells that fuse share all of the information they
contain
Nuclear fusion leads to new genotypes
Used to study genomic interactions; cytoplasmic
regulation of cell biology
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
28/82
11/25/2013 nur anisah 28
* The simplest organisms must be able to communicate.
* Most commonly such communication mediates mating.
* As multicellular organisms developed and differentgroups of cells took on different functions, it became
necessary for cells to communicate many aspects of
their status.
* Some groups of cells also took on the role of controlling
the behaviour of other groups of cells.
We can define three types of intercellular signaling in the human
body:
Endocrine - Cells in one part of the body send hormones via thebloodstream to influence other parts
Paracrine - Cells secrete substances that influence other cells around
them
Autocrine - Cells secrete substances that influence themselves
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
29/82
11/25/2013 nur anisah 29
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
30/82
11/25/2013 nur anisah 30
* Thus it should be clear that these types of intercellular
signaling are defined by the distance between the signaling
cell and its target cell.
* Intercellular signaling can also be classified based uponthe way in which the signaling cells molecules impact the
target cells.
* These are called modes of intercellular communication.
In spite of the complexity of the human body and thediversity of intercellular communications that occur, the
modes of cellular communication can be classified into four
major groups:
1. Communication via Diffusible Molecules2. Communication via Cellular Continuities
3. Communication via Cell Contact
4. Communication mediated by the Extracellular Matrix
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
31/82
11/25/2013 nur anisah 31
1. Communication via Diffusible Molecules
Communication via diffusible molecules involves a secretor,
a cell or group of cells that secrete the signaling molecule,
and a responder, a target cell or group of cells that detect
the signal and transduce it into a response.
To be able to respond to another cell's signal, theresponding cell needs to possess a specific receptor that
recognizes the secreted molecule which is generally termed
a ligand. While there are many hormones in the human
body, only certain cell types have the appropriate receptorfor them.
Those receptors may lie at the surface of the cell or they
may reside in the cytoplasm.
1. Communication via Diffusible Molecules
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
32/82
11/25/2013 nur anisah 32
Diffusible Molecules: Surface Receptors
These are typically water soluble molecules (i.e., can't diffuse through the
lipid bilayer)
Peptide hormones & growth factors; neurotransmitters, etc. are typical
examples
Regulate the cell's physiology in the short-term; can regulate gene activity
in the long term
Lead to intracellular signalling events often involving calcium ions, cAMP,
protein phosphorylation, etc.
This topic will be the focus of the lectures on signal transduction
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
33/82
11/25/2013 nur anisah 33
Diffusible Molecules: Intracellular Receptors
Lipid soluble molecules which can diffuse across the lipid bilayer
E.g., sex hormones: estrogen & progesterone; pheromones
Diffuse into cell, bind to cytoplasmic receptor which migrates into
nucleus to regulate gene activitynot covered in this course.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
34/82
11/25/2013 nur anisah 34
2. Cellular Continuities
Unspecialized: Plasmodesmata of plants and connections between
cleavage cells of the early embryo; these are so large in plants that oftenorganelles can pass from one cell to the next
Specialized: These are typified by Gap Junctions which allow the electrical
or physiological coupling of cells by the intercellular diffusion of small
molecules (i.e., ions, cAMP, cGMP, etc.)
2. Communication via Cellular Continuities
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
35/82
11/25/2013 nur anisah 35
3. Contact-Mediated
Cell adhesion leads to cellular responses; like receptor-ligand binding
E.g., "Contact inhibition of movement"; Sperm-Egg binding sets up
change of Rx for fertilization
3. Communication via Cell Contact
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
36/82
11/25/2013 nur anisah 36
ECM-Mediated
When it was first studied, the
extracellular matrix (ECM) wasconsidered to be simply a
supporting matrix
for cells and tissues. It is clear
now that the ECM affects the
way cells behave and how they
communicatewith each other. The role of the
ECM in cell adhesion was
discussed earlier and will be
covered again in
future lectures on chemotaxis,
among others.
ECM exists between all cells in tissues
Network of proteins & carbohydrates
ECM specialized as basal lamina, basement membrane
Regulates intercellular communication
4. Communication mediated by the Extracellular Matrix
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
37/82
11/25/2013 nur anisah 37
Role of ECM in Morphogenesis
Historically, one of the best examples of the function of the ECM
in intercellular communication has come from studies on the
development of secretory glands such as the mammary glands
and salivary glands.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
38/82
11/25/2013 nur anisah 38
The experiments below show how the removal of the ECM
prevents the branching of the salivary gland.
Once the ECM reforms, the branching process then occurs.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
39/82
11/25/2013 nur anisah 39
L ecture Outline
Action of Surface Receptors Four Classes of Surface Receptors
Ion Channel Linked Receptor
Enzyme Receptors
Guanylate Cyclases Receptor Tyrosine Kinases
Cytokine-Receptor Superfamily
G-Protein Coupled Receptor (GPCR)
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
40/82
11/25/2013 nur anisah 40
Action of Surface Receptors
When a membrane impermeable ligand (e.g., a peptide
hormone) binds to its receptor, it activates the receptor. This
activation typically involves a conformational change in the
protein (e.g., it undergoes changes in the folding of its primary
amino acid chain in one or more regions). This conformational
change has different implications depending on the receptor and
ligand.
For example, it may allow the receptor/ligand to bind to otherproteins (e.g., enzymes) forming an activated receptor complex.
The activated receptor complex then activates downstream
effectors (enzymes) that in turn lead to changes in the
physiology, behavior or shape of the cell. Or it may directly lead
to the activation of transcription factors that will enter the
nucleus to regulate gene activity. Long-term stimulation can leadto physiological changes in the cell that can also lead to the
activation of gene activity. As we progress through the next few
lectures, we'll learn exactly what kinds of events are occurring at
each stage in the process.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
41/82
11/25/2013 nur anisah 41
Four Classes of Surface Receptor
There are four major classes of surface
receptors:
Ion Channel Linked Receptor
Enzyme Linked Receptor
G-Protein Coupled Receptor
Tyrosine Kinase-Linked Receptor
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
42/82
11/25/2013 nur anisah 42
Ion Channel L inked Receptor
Receptor is an ion channel
Ligand binds to & opens channel
Ions flow into cell binding to and activating various proteins E.g., Neurotransmitter-gated ion channels
Acetylcholine (Ach) binds to receptor and opens Na+/K+ channels
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
43/82
11/25/2013 nur anisah 43
Enzyme Receptors
Ligand activates enzymatic receptor directly (i.e., the
receptor is an enzyme)
3 Main types:
1. Ser/Thr Kinases - enzymes that phosphorylate serine
&
threonine on proteins
2. Protein Tyrosine Kinases (TKs) or Receptor TKs (RTKs)-
enzymes that phosphorylate tyrosine residues
3. Guanylate Cyclases (GCs) - enzymes generate cyclic
GMP from GTP
RTKs mediate actions of most growth factors (EGF, NGF,
PDGF, etc.); therefore of great interest for their
role in cancer (discussed in detail in a future
lecture)
G l t C l
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
44/82
11/25/2013 nur anisah 44
Guanylate Cyclases
As shown in the above figure, when bound to its ligand, guanylate cyclase receptors become activated.
Active guanylate cyclase converts guanosine trisphosphate (GTP) into cyclic 3',5' guanosine monophosphate(cGMP).While cyclic AMP (cAMP) has received the most attention over the years, its younger biochemical
sibling, cyclic 3',5' guanosine monophosphate (cGMP) also plays some important roles in cellular function.
Generally cAMP and cGMP mediate opposing events. In blood vessels, cGMP mediates muscle relaxation
leading to vessel dilation. cGMP activates specific cGMP-dependent kinases in many cell types. cGMP also
regulates ion channels in the rods of the eye.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
45/82
11/25/2013 nur anisah 45
Receptor Tyrosine Kinases
A typical receptor tyrosine kinase receptor (RTK: e.g., epidermal growth
factor receptor, EGFR) binds to its
ligand resulting in dimerization and enzyme activation. The receptor/ligand
complex then phosphorylatesitself leading to the further activation of the receptor complex allowing it to
phosphorylate tyrosine residues
on it target proteins.
Some RTKs include those that
bind to epidermal growth factor
(EGF), nerve growth factor(NGF), fibroblast
growth factor (FGF) and platelet
derived growth factor (PDGF).
Later in the course, we will focus
on EGF
and EGFR signal transductionand its role in cell motility and
invasiveness in cancer cells.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
46/82
11/25/2013 nur anisah 46
Cytokine-Receptor Superfamily
Unlike RTKs that have intrinsic enzyme activity, members of the cytokine-receptor
superfamily are not
tyrosine kinases. They are tyrosine kinase-linked receptors. Cytokine-receptors must
first dimerize and thenbind to cytoplasmic tyrosine kinases before they are able to phosphorylate their
target proteins. As their
name implies, they are activated by cytokines. They are also activated by interferons
and human growth
factor (HGF).
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
47/82
11/25/2013 nur anisah 47
G-Protein Coupled Receptor (GPCR)
G-Protein Coupled Receptors (GPCR) are among the most-studied
receptors.
Also called G-Protein Linked Receptor (GPLR)
Receptor & effector use G protein intermediary
Ligand binds receptor
Ligand/Receptor complex binds G protein
G protein is activated and binds to effector
Effector channel opens or enzyme is activated
In the next few lectures, we'll look at the G protein cycle and GPCR
signaling in more detail.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
48/82
11/25/2013 nur anisah 48
Plasma Cell Membrane
Cl ifi i f i ll l i i
http://rds.yahoo.com/_ylt=A9G_Rq8KxL1EWakAaxWjzbkF;_ylu=X3oDMTA4NDgyNWN0BHNlYwNwcm9m/SIG=12ua2sstl/EXP=1153373578/**http%3a/sun.menloschool.org/~dspence/biology/chapter5/images/membrane.jpg -
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
49/82
Many cell signals are
- carried by molecules that are released by one cell andmove to make contact with another cell.
Endocrine system#Types of signaling
Within endocrinology(the study of intercellular signalling in animals)
and the endocrine system, intercellular signalling is subdivided into
the following classifications:
Endocrinesignals are called hormones.
Hormones are produced by endocrine cells and they
travel through the bloodto reach all parts of the body.
Specificity of signaling can be controlled if only some cellscan respond to a particular hormone.
Paracrine signals target only cells in the vicinity of the emitting
cell. Neurotransmittersrepresent an example.
11/25/2013 nur anisah 49
Classification of intercellular communication
http://en.wikipedia.org/wiki/Endocrine_systemhttp://en.wikipedia.org/wiki/Endocrinologyhttp://en.wikipedia.org/wiki/Endocrine_systemhttp://en.wikipedia.org/wiki/Endocrine_systemhttp://en.wikipedia.org/wiki/Hormonehttp://en.wikipedia.org/wiki/Circulatory_systemhttp://en.wikipedia.org/wiki/Paracrine_signallinghttp://en.wikipedia.org/wiki/Neurotransmittershttp://en.wikipedia.org/wiki/Neurotransmittershttp://en.wikipedia.org/wiki/Paracrine_signallinghttp://en.wikipedia.org/wiki/Circulatory_systemhttp://en.wikipedia.org/wiki/Hormonehttp://en.wikipedia.org/wiki/Endocrine_systemhttp://en.wikipedia.org/wiki/Endocrine_systemhttp://en.wikipedia.org/wiki/Endocrinologyhttp://en.wikipedia.org/wiki/Endocrine_systemhttp://en.wikipedia.org/wiki/Endocrine_systemhttp://en.wikipedia.org/wiki/Endocrine_systemhttp://en.wikipedia.org/wiki/Endocrine_system -
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
50/82
Neurotransmitters represent an example.
Some signaling molecules can function as both a hormone and
a neurotransmitter.
For example, epinephrineand norepinephrinecan function ashormones when released from the adrenal glandand are
transported to the heart by way of the blood stream.
* Norepinephrine can also be produced by neuronsto
function as a neurotransmitter within the brain.
Autocrinesignals affect only cells that are of the same cell type as theemitting cell.
- An example for autocrine signals is found in immune cells.
Estrogencan be released by the ovaryand function as a hormone or act
locally via paracrine or autocrinesignaling.
Juxtacrinesignals are transmitted along cell membranes via protein or
lipid components integral to the membrane and are capable
of affecting either the emitting cell or cells immediately
adjacent.
nur anisah 5011/25/2013
http://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Epinephrinehttp://en.wikipedia.org/wiki/Norepinephrinehttp://en.wikipedia.org/wiki/Adrenal_glandhttp://en.wikipedia.org/wiki/Neuronhttp://en.wikipedia.org/wiki/Autocrine_signallinghttp://en.wikipedia.org/wiki/Immune_cellhttp://en.wikipedia.org/wiki/Estrogenhttp://en.wikipedia.org/wiki/Ovaryhttp://en.wikipedia.org/wiki/Autocrinehttp://en.wikipedia.org/wiki/Juxtacrine_signallinghttp://en.wikipedia.org/wiki/Juxtacrine_signallinghttp://en.wikipedia.org/wiki/Autocrinehttp://en.wikipedia.org/wiki/Ovaryhttp://en.wikipedia.org/wiki/Estrogenhttp://en.wikipedia.org/wiki/Immune_cellhttp://en.wikipedia.org/wiki/Autocrine_signallinghttp://en.wikipedia.org/wiki/Neuronhttp://en.wikipedia.org/wiki/Adrenal_glandhttp://en.wikipedia.org/wiki/Norepinephrinehttp://en.wikipedia.org/wiki/Epinephrinehttp://en.wikipedia.org/wiki/Neurotransmitter -
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
51/82
11/25/2013 nur anisah 51
- How Cells Communicate with
Each Other
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
52/82
11/25/2013 nur anisah 52
Human communication
Consider how a message is sent over the
telephone:
One person speaks into a receiver
that convertsthe sound into
an electrical signal, which can then be transmitted
over great distances before being
converted back into sound at its
destination.
This process retains the original content of
the message and is called signal
transduction.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
53/82
11/25/2013 nur anisah 53
The signals sent by cells are far simpler
than the highly complex messages used
by humans.
One cell,
termed the signaling cell
produces a particular chemical molecule
that is detected by another cell
the receiving cell
using a receptor protein that recognizes
the molecule and respondsspecificallyto it.
The protein, acting as the receptor, is the first step in which the chemical
signal present on the outside of the cell will be converted(transduced) to different signals inside the cell.
These signals will subsequently direct cell behavior.
This conversion, a biologically evolved form of signal transduction,
that is the essential element that allows a cell to communicate.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
54/82
11/25/2013 nur anisah 54
an EXAMPLE of COMMUNICATION... CELL to CELL SIGNALING SYSTEMS
sex-A ["a"-cell : releases a-factor (peptide of 12 aa's) - binds to sex-B receptors]
sex-B [""-cell : releases -factor - binds to sex-A receptors]
results = is fusion of 2 cells (mating) producing diploid cell.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
55/82
11/25/2013 nur anisah 55
Figure 2. Types o f sig nals.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
56/82
11/25/2013 nur anisah 56
T f i t ll l i ti i
http://www.colorado.edu/intphys/Class/IPHY3430-200/image/06-2.jpghttp://www.colorado.edu/intphys/Class/IPHY3430-200/image/06-2.jpg -
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
57/82
11/25/2013 nur anisah 57
Types of intercellularcommunication--review
http://www.colorado.edu/intphys/Class/IPHY3430-200/image/06-2.jpghttp://www.colorado.edu/intphys/Class/IPHY3430-200/image/06-2.jpg -
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
58/82
11/25/2013 nur anisah 58
PARACRINE (local) SIGNALINGlocal regulator chemical messengers are
targeted to specific receptors
often includes: growth factor proteins thatpromote cell division & growth
& neurotransmittersthat move across
synapses to other neurons
ENDOCRINE(distant) SIGNALINGspecialized cells release molecules (often
hormones) into blood vessels of circulatory
system, hormones move to distant targetcells... elicit response
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
59/82
11/25/2013 nur anisah 59
gap junctions & plasmodesma...results in cytoplasmic continuity favoring cellular interactions...
Communication via CELL-TO-CELL CONTACT
- here the signaling is direct:
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
60/82
11/25/2013 nur anisah 60
cell surface contacts...receptor protein specificity (as above with yeast cells)...
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
61/82
11/25/2013 nur anisah 61
A. Some of the basic characteristics of cell signaling
- Cell must respond appropriately to external stimuli to survive.
- Cells respond to stimuli via cell signaling
The Overall Flow of Information During Cell Signaling.
Binding of ligand by a receptor activates a series of events known as signal transduction,
which relays the signal to the interior of the cell, resulting in specific cellular responses and/or changes I
n gene expression.
Signal transduction pathways consist of a series of steps
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
62/82
11/25/2013 nur anisah 62
Recognition of the stimulus by
a specific plasma membrane
receptor.
Transfer of a signal across the
plasma membrane.
Transmission of the signal to
effector molecules within the
cell, which causes a change in
cellular activities.
Cessation of the cellular
response due to inactivation of
the signal molecule.
Signal transduction pathways consist of a series of steps
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
63/82
11/25/2013 nur anisah 63
B. The forms of cell communication ---Different types of chemical signals
can be received by cells
C. Signal Molecules and Receptors signal molecules:
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
64/82
11/25/2013 nur anisah 64
C. Signal Molecules and Receptors signal molecules:
(1) Lipid-soluble hormones
(2) Water-soluble hormones
(3) nitric oxide (NO) and carbon monoxide(CO) as cellular messengers
Receptors include two classes: glycoproteins
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
65/82
11/25/2013 nur anisah 65
Different cells can respond differently to the same extracellular
signal molecule
Various responses induced by neurotramsmitter acetylcholine
Each cell is programmed to respond to specific combinations of extra
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
66/82
11/25/2013 nur anisah 66
Each cell is programmed to respond to specific combinations of extra
cellular signal molecules
Apoptosis ----controlled cell suicide for infected or damaged cells, or cells at end of
functional life span: cells are disposed of in an orderly fashion without damage to
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
67/82
11/25/2013 nur anisah 67
functional life span: cells are disposed of in an orderly fashion, without damage to
neighboring cells
Apoptosis ----controlled cell suicide for infected or damaged cells, or cells at end of
functional life span: cells are disposed of in an orderly fashion without damage to
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
68/82
11/25/2013 nur anisah 68
functional life span: cells are disposed of in an orderly fashion, without damage to
neighboring cells
1. ReceptionWhen reception occurs at the plasma membrane,
a chemical message binds to a protein on the cell surface.
A signal molecule binds to a receptor protein, causing the
protein to change shape.A cell targeted by a particular chemical signal has molecules of
a receptor protein that recognizes the signal molecule.
The signal molecule is complementary in shape to a specific site
on the receptor and attaches there, like a key in a lock.
... is not unlike recognition of enzyme for its substrate [ES complex]
... akin to the lock-&-key hypothesis of enzyme-substrate recognition
... ligand molecules (usually water soluble) are recognized byonly one receptor protein bound within a cell membrane
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
69/82
11/25/2013 nur anisah 69
SIGNAL TRANSDUCTION
2 T d ti
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
70/82
11/25/2013 nur anisah 70
2. Transduction
The binding of the signal molecule altersthe receptor protein in some way.
The signal usually starts a cascade of reactions
known as a signal transduction pathway
Transduction stage is usually a pathway
of several steps, with each molecule in the
pathway bringing about a change in the next.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
71/82
11/25/2013 nur anisah 71
leads to a conformation change in receptor
shape change results in receptor interacting with other
intra-cellular molecules
may result in multiple conformational/structural changes
in other cellular proteins inactive enzymes ---> active enzymes,
& so on, etc...
2. Transduction
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
72/82
11/25/2013 nur anisah 72
3. Response
The transduction pathway finally triggers a response
The responses can vary from turning on a gene,activating an enzyme, rearranging the cytoskeleton
There is usually an amplification of the signal (one
hormone can elicit the response of over
108molecules
The last molecule in the pathway triggers the cell's
response.
... usually a cellular activity, as enzyme catalysis, or
the rearrangement of cytoskeleton (movement),
or specific gene activity.
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
73/82
11/25/2013 nur anisah 73
a signal moleculebinds to a receptor --> conformation change -->an inactive G-(GDP)-proteinnow binds GTP (replacing GDP)...
fig 11.7a*
http://fig.cox.miami.edu/~cmallery/150/memb/fig11x6a.jpghttp://fig.cox.miami.edu/~cmallery/150/memb/fig11x6a.jpg -
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
74/82
11/25/2013 nur anisah 74
and active G-(GTP)-proteinstimulates other inactive enzymes.fig 11.7b*
http://fig.cox.miami.edu/~cmallery/150/memb/fig11x6b.jpghttp://fig.cox.miami.edu/~cmallery/150/memb/fig11x6b.jpg -
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
75/82
11/25/2013 nur anisah 75
* Mediated by the Ion-Linked Receptors which convert chemical signals
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
76/82
11/25/2013 nur anisah 76
y p g
into electrical ones
4 or 6-helix transmembrane receptor
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
77/82
11/25/2013 nur anisah 77
Activation of G proteins
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
78/82
11/25/2013 nur anisah 78
The cells in our body communicate with each other exchanging
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
79/82
11/25/2013 nur anisah 79
The cells in our body communicate with each other, exchanging
information, via certain frequencies or electrical impulses.
In a healthy body, this exchange of information between the
cells functions unhindered and each cell or part of the body canfulfill its role in the regulatory process, keeping you running like
a well-oiled machine.
Cells communicate via frequencies.
Substances causing a stress load on the body can muck up
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
80/82
11/25/2013 nur anisah 80
g y p
communication between cells.
If interfering substances (toxins, viruses, bacteria etc) are able
to affect the body, their disruptive frequency patterns can upsetthe communication between the cells.
Cells are unable to communicate
Di t b d ll i ti lt i i ( h i l)
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
81/82
11/25/2013 nur anisah 81
Disturbed cell communication can result in organic (physical)
changes.
If communication between the cells is disturbed, they cant perform their
intended function properly and we get something akin to a malfunction ofthe regulatory systems.
The evidence of this could be seen to varying degrees in, for instance, non-
specific, disturbed wellbeing, physical exhaustion and debilitating fatigue.
Exhaustion could be a symptom
-
7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor
82/82
Maturnuwun
top related