dr.nur anissah ans-uii 2okt'09 komunikasi seluler&konsep reseptor

7/22/2019 Dr.nur Anissah Ans-UII 2Okt'09 Komunikasi Seluler&Konsep Reseptor

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Komunikasi seluler dan

Konsep reseptor

Nur Anisah

Bagian Histologi&BiologiSel

Facultas Kedokteran

Universitas Gadjah Mada

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http://en.wikipedia.org/wiki/File:Community_of_Cells.jpg


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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)


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Komunikasi interseluler :

MOLEKUL SINYAL : * Asam amino

* Polipeptida* Steroid

* Mikromolekul

Misal: - Hormon

- Sitokin

- Growth factor- Neurotransmitter

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Molekul sinyal

Fungsi : Sebagai ligan: akan mengubah konfigurasi

protein penyusun reseptor yg diikatnya


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Pesan dari sel lain :

Memproduksi suatu protein tertentu

Mengeluarkan suatu produk ke luar sel

Merubah bentuk sel

Supaya sel berpindah ke tempat lain


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TIPE KOMUNIKASI ANTAR-SEL:

1. KOMUNIKASI LANGSUNG (Direct

Communication) Junctional

complexes / gap junctions

2. KOMUNIKASI TIDAK LANGSUNG (Indirect

Communication) Menggunakanbeberapa macam molekul sinyal


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Epithelial cells communicate and adhere

to each other and/or to the underlyingbasement membrane by diverse junctions.

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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.


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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.


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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.


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HUBUNGAN ANTAR-SEL

Bangunan khusus pada permukaan sel

Apical

Lateral

Basal


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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.


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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


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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.

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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


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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.


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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.


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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.


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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.


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The gap junction will be discussed in more detail in the lecture on cell

communication.


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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


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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.


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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).

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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)


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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.

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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.

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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


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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


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* 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


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* 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


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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


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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


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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.


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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


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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


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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


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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.


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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.


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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)


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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.


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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


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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


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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


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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.


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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.


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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).


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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.


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Plasma Cell Membrane

Cl ifi i f i ll l i i
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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.

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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


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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


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- How Cells Communicate with

Each Other


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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.


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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.


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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.


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Figure 2. Types o f sig nals.


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T f i t ll l i ti i
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Types of intercellularcommunication--review
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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


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gap junctions & plasmodesma...results in cytoplasmic continuity favoring cellular interactions...

Communication via CELL-TO-CELL CONTACT

- here the signaling is direct:


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cell surface contacts...receptor protein specificity (as above with yeast cells)...


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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


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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


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B. The forms of cell communication ---Different types of chemical signals

can be received by cells

C. Signal Molecules and Receptors signal molecules:


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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


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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


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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


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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


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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


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SIGNAL TRANSDUCTION

2 T d ti


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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.


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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


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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.


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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


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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


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* Mediated by the Ion-Linked Receptors which convert chemical signals


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y p g

into electrical ones

4 or 6-helix transmembrane receptor


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Activation of G proteins


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The cells in our body communicate with each other exchanging


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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


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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)


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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


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