cell to cell communication

8/2/2019 Cell to Cell Communication - 1

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CELL TO CELL

COMMUNICATION - 1

Dr. Dinesh Kumar

Department of Life Sciences

International Medical University

HUMAN BIOLOGY


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Learning Objectives

At the end of this lecture you should beable:

to know about cellular junctions to understand ligand-receptor concept

to know about receptor linked channels

and G-proteins


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Cell Communication

Cells communicate with one anotherin complex ways to govern their ownbehavior for the benefit of theorganism as a whole.

Cell communications depend onextracellular signal molecules whichare produced by cells to signal to

their neighbors or to cells furtheraway.


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Cell communication - Example

Signalmolecule

Distant

Cell


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How do cells communicate?


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How do cells communicate?

The process must involve three stages.

In reception, a chemical signal binds to acellular protein (receptor), typically at the cellssurface.

In transduction, binding leads to a change inthe receptor that triggers a series of changesalong a signal-transduction pathway.

In response, the transduced signal triggers a

specific cellular activity.


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1. Membrane junctions

Usually there is a space between plasma

membranes of adjacent cells, filled withextracellular fluid and provides pathway forsubstances to pass between cells.

This space is called as a junction. Cells within a tissue are connected to each

other by cell junctions or otherwise called

as membrane junctions.


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Membrane/cellular junctions

Desmosomes

Tight junctions

Gap junctions

Adherens junctions


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Desmosomes

Consist of a region between two adjacent cellsseparated by 20 nm. Have a dense accumulation of protein at cytoplasmic

surface of each membrane and in the space between thetwo membranes.

Protein fibers extend from cytoplasmic surface ofdesmosomes across the cell and are Linked to other desmosomes on opposite side of the cell.

Desmosomes function to hold adjacent cells firmlytogether Subject to considerable stretching Eg. Skin cells.


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Desmosomes


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Tight junctions

They are impermeable junctions

Most epithelial cells are joined by tight junctions. A series of protein molecules in plasma membranes of

adjacent cells fuse together.

They prevent molecules passing through extracellular space

between cells.

Eg: tight junctions between epithelial cells liningdigestive tract

Keep digestive enzymes and microorganisms in theintestine from seeping into bloodstream.


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Tight junction


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Gap junctions

Membrane junctions allow chemical messengers fromone cell to another cell. Communicating junctions between adjacent cells.

At gap junctions adjacent plasma membranes are

very close & cells are connected by connexonscomposed of transmembrane proteins.

Ions, simple sugars & small molecules pass throughthem.

Present in electrically excitable tissues, such as heart& smooth muscle.


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Gap junction


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Adherens junctions

Adherens junctions provide strong mechanicalattachments between adjacent cells.

They hold: cardiac muscle cells tightly together as the heart

expands and contracts. epithelial cells together.

Adherens junctions are composed of the followingproteins: Cadherins are transmembrane proteins (shown in

red) whose

extracellular segments bind to each other and whose intracellular segments bind to catenin

Catenin (yellow) which are connected to actin filaments


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Adherens junction


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Membrane junctions


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Ligand-Receptor concept

Ligand: Signaling chemicals or first messengers Any molecule or ion bound to specific sites on the surface

of a protein. That bind specifically to membrane proteins or receptors.

Chemical messengers: are various hormones, transmitters& other mediators.

Membrane receptors: Group of integral proteins.

Receptors are the sensing elements in the system ofchemical communications and coordinates the function ofall different cells in the body.

Protein binding site: region of a receptor protein to whicha ligand binds.


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Properties of a protein binding site

Chemical specificity

Affinity

Saturation Competition


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Affinity

Is the strength of ligand-protein binding.

High affinity

Intermediate affinity

Low affinity

Affinity & chemical specificity are two distinct,properties of binding sites.

Chemical specificity depends on shape of binding site

Affinity depends on strength between protein &ligand.


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Affinity

Three binding sites with the

same chemical specificityfor a ligand but differentaffinities.


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Saturation

The fraction of total binding

sites occupied at anygiven time.

When all binding sites

occupied, The population of binding

sites is 100% saturated.

When half the availablesites are occupied,

The system is 50%saturated & so on.


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Competition

More than one type of ligand can bind to

certain binding sites.

Competition occurs between ligandsfor the same binding site.

Presence of multiple ligands, to bindthe same binding site affects the % of

binding sites occupied by any oneligand.


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Competition


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Role of membrane receptors

Some function in contact signaling & others in chemicalsignaling. Contact signaling- the actual touching of cells

By which cells recognize one another. Important for normal development & immunity.

Some bacteria & infectious agents use contact signaling To identify its target tissues or organs.

Most plasma membrane receptors are involved in chemicalsignaling Signaling chemicals or ligands bind specifically to plasma membrane

receptors

Different cells respond differently to the same ligand. Eg: Acetylcholine stimulates skeletal muscle cells to contract, but

inhibits heart muscle.


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Modes of communication

There are four basic mechanisms for

cellular communication:

1. Direct contact 2. Paracrine signaling

3. Endocrine signaling

4. Synaptic signaling


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Direct contact

In direct contact the

molecules on thesurface of one cell arerecognized by

receptors on theadjacent cell


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Paracrine signaling

Here the signal

released from a cellhas an effect onneighboring cells


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Endocrine signaling

In endocrine

signaling thehormones releasedfrom a cell affect

other cellsthroughout thebody.


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Synaptic signaling

In this type the

nerve cells releasethe signal(neurotransmitter)

which binds toreceptors onnearby cells.


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PLASMA-MEMBRANE RECEPTORS

For lipidinsoluble messengers

Receptors that function as ion channels.

Receptors that function as enzymes.

Receptors that activate G proteins

Which in turn act upon effector proteins -either ion channels or enzymes in the plasmamembrane.

Types of receptors


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Protein that acts as the receptor itself constitutes an

ion channel

Activation of the receptor by a first messengercauses the channel to open (voltage-gated channelsand ligand-gated channels)

Highly selective for transport of ions or molecule

Results in an increase in net diffusion across the

plasma membrane of the ion or ions specific tothe channel.

They respond to changes in membrane potentialby opening or closing the channel (voltage-gatedchannels)

Receptors Ion channels


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Such a change in ion diffusion

changes membrane potential & causes electrical signaling.

This electric signal is the essentialevent in cells response to themessenger.

Common in excitable tissues(neural & muscle)



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Chemical (ligand) gating

Some protein channel gates are opened by

binding of a chemical substance (a ligand)with protein.

This causes a conformational or chemical change inthe protein molecule.

that opens or closes the gate.

This is called chemical gating or ligand gating.

Gating of protein channels


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Many PM receptors possess intrinsic enzyme activity & allare protein kinases.

They all involve in activation of cytoplasmicproteins by phosphorylation.

The binding of a specific messenger to the receptorchanges

Conformation of the receptors enzymatic portion,on cytoplasmic side of PM & activates receptor. This results in autophosphorylation (addition of

phosphate group) of the receptorand phosphorylates its own tyrosine groups.

The newly created phosphotyrosines oncytoplasmic portion serve as docking sites forcytoplasmic proteins.

Enzyme linked receptors


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The bound docking proteins then bind otherproteins

Leads to a cascade of signaling pathways withinthe cell.

Large number of kinases mediate thesephosphorylations.

At the end of these sequences the ultimatephosphorylation of key proteins underlies

The cells response to the original firstmessenger.

Enzyme linked receptors


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These are transmembrane receptors coupled tointracellular effector systems via a G-protein

A protein bound to this receptor on insidesurface (cytosolic) of the PM - called G

proteins.

Their characteristic structure comprises:

Seven transmembrane spanning helices

With an extra-cellular N-terminal domain &An intra-cellular C-terminal domain.

Receptors with G proteins


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G-proteinsWhose function is to

recognize activated GPCRs & Pass the message to effector

systems (secondmessengers) that generate acellular response.

G-proteins consist of 3

subunits: , & .

Guanosine triphosphate(GTP) binds to the subunit

has enzymic activity,catalyzing the conversion ofGTP to GDP.



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The and subunits remain together as a complex.

All 3 subunits (, & ) are anchored to theplasma membrane

The binding of a first messenger to the receptor

changes the conformation of the receptor.

This change causes one of the three subunits of theG protein to link up with another PM protein either an ion channel or an enzyme.



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The G protein may cause the ion

channel to open, with resultinggeneration of electric signals.

G protein may activate or inhibit themembrane enzyme with which it

interacts & generation of secondmessengers inside the cell.



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G protein coupled receptors (GPCRs) - exert theireffect indirectly through a G protein

Acts as or relay to activate (or inactivate) amembrane-bound enzyme or ion channel.

G-proteins are freely diffusible in the plane of themembrane,

A single pool of G-protein in a cell can interactwith several different receptors & effectors.



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1.Rang & Dales Pharmacology, 6th editionchapter 3

2. Molecular Biology of Cell, 5th edition ,

Alberts, Johnson, Lews, Raff, Roberts,Walter

References

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