Overview: The Cellular Internet

• Cell-to-cell communication is essential for organisms

• Biologists have discovered some universal strategies and mechanisms of cellular regulation

• Response is determined by combined effects of multiple signals

Yeast Mating-a classic system

Receptor factor

a factor

a

a

Exchangeof matingfactors

Yeast cell,mating type a

Yeast cell,mating type

Mating

New a/cell

a/

1

2

3

An example of cell signalling

• Yeast Mating System Exemplifies Cell Communication

• Aka Signal Transduction

• Simple but all the key features are present

• Reception, Transduction, Response

• A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response

• Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes

• The concentration of signaling molecules allows bacteria to detect population density

• Quorum-sensing in Vibrio fischerii

When cells aretouching signalling is easy

Plasma membranes

Gap junctionsbetween animal cells

(a) Cell junctions

Plasmodesmatabetween plant cells

(b) Cell-cell recognition

• In many other cases, cells must share information with cells they are not touching

• They use (1) local regulators, messenger molecules that travel only short distances

• And (2) chemicals called hormones for long-distance signaling

Local signaling in animals is either paracrine or synaptic

Local signaling

Target cell

Secretoryvesicle

Secretingcell

Local regulatordiffuses throughextracellular fluid

(a) Paracrine signaling (b) Synaptic signaling

Target cellis stimulated

Neurotransmitter diffuses across synapse

Electrical signalalong nerve celltriggers release ofneurotransmitter

Both are short-range but synaptic signaling occurs only in the nervous system

Long-distance signaling usually involves different organs communicating

Endocrine cell Bloodvessel

Hormone travelsin bloodstreamto target cells

Targetcell

(2) Hormonal signaling

The messenger molecules are called hormones

EXTRACELLULARFLUID

Plasma membrane

CYTOPLASM

Receptor

Signalingmolecule

Relay molecules in a signal transduction pathway

Activationof cellularresponse

Transduction Response2 3Reception1

There are three stages in cell signaling

Reception

Transduction

Response

RECEPTIONTRANSDUCTION

RESPONSE

• The binding between a signal molecule (ligand) and receptor is highly specific

• A shape change in a receptor is often the initial transduction of the signal

• Most signal receptors are plasma membrane proteins

• 3 examples from many possible

• A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein

• The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive

• GTP/GDP are chemically very similar to ATP/ADP but contain Guanine not Adenine

Reception- Example I

Mechanism of G protein coupled reception

G protein-coupledreceptor

Plasmamembrane

EnzymeG protein(inactive)

GDP

CYTOPLASM

Activatedenzyme

GTP

Cellular response

GDP

P i

Activatedreceptor

GDP GTP

Signaling moleculeInactiveenzyme

1 2

3 4

The relay protein is called a “G Protein”

• Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines

• Has intra- and extracellular domains, also membrane domain

• A receptor tyrosine kinase can trigger multiple signal transduction pathways at once

• Kinase is an enzyme that attaches a phosphate to a substrate

Reception- Example II

Signalingmolecule (ligand)

Ligand-binding site

Helix

TyrosinesTyr

Tyr

Tyr

Tyr

Tyr

Tyr

Receptor tyrosinekinase proteins

CYTOPLASM

Signalingmolecule

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Dimer

Activated relayproteins

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P

P

P

P

P

P

Cellularresponse 1

Cellularresponse 2

Inactiverelay proteins

Activated tyrosinekinase regions

Fully activated receptortyrosine kinase

6 6 ADPATP

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P

P

P

P

P

P

1 2

3 4

• A ligand-gated ion channel receptor acts as a gate when the receptor changes shape

• When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

Reception- Example III

Ligand-gated ion channel

Signalingmolecule(ligand)

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed3

2

1

SignalTransduction

:

an exampleof a keytype oftransductionpathwayand responseAn example

of a response

Reception

Transduction

Response

Binding of epinephrine to G protein-coupled receptor (1 molecule)

Inactive G protein

Active G protein (102 molecules)

Inactive adenylyl cyclaseActive adenylyl cyclase (102)

ATPCyclic AMP (104)

Inactive protein kinase AActive protein kinase A (104)

Inactive phosphorylase kinase

Active phosphorylase kinase (105)

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106)

GlycogenGlucose-1-phosphate

(108 molecules)

This type of signal transduction pathway is called a cascade

Cyclic AMP is the key inside the cell.(Do not

memorize this cascade)

Adenylyl cyclase

Pyrophosphate

P P i

ATP cAMP

Phosphodiesterase

AMP

Cyclic AMP is the “second messenger”

Ethylene Response in plants

Identify: Reception, Transduction, Response