Cell Communication

Cell-to-cell communication is important for multicellular organisms

Exchange ofmating factors

Mating

Receptor

a

factor

a

a factorYeast cell,mating type a

Yeast cell,mating type

a/

New a/ cell

https://www.youtube.com/watch?v=TfpOKWdOolM

(Start at 3:40 - ~ 6:00) https://www.youtube.com/watch?

v=DY3SQA79ZVo (only 1 second)

chemical messengerscell junctions directly connect adjacent cells

In local signaling, animal cells may communicate by direct contact

Plasma membranes

Gap junctionsbetween animal cells

Cell junctions

Cell-cell recognition

Plasmodesmatabetween plant cells

Animals use local regulators (for short distance signals)◦EX: Humans: pass a note; text message; Celly; email; Facebook

Plants and animals use chemicals called hormones (for long distance)

Paracrine signaling

Local regulatordiffuses throughextracellular fluid

Secretoryvesicle

Secretingcell

Target cell

Local signaling

Electrical signalalong nerve celltriggers release ofneurotransmitter

Neurotransmitter diffuses across synapse

Endocrine cell Bloodvessel

Long-distance signaling

Hormone travelsin bloodstreamto target cells

Synaptic signaling

Target cellis stimulated

Hormonal signaling

Target cell

http://www.bozemanscience.com/037-cell-communication

Earl Sutherland discovered how the hormone epinephrine acts on cells

http://media.pearsoncmg.com/bc/bc_campbell_biology_7/mm2/ch11/InstructorResources/medialib_tab_2/1.htm

◦Reception◦Transduction◦Response

◦ http://media.pearsoncmg.com/bc/bc_campbell_biology_7/mm2/ch11/InstructorResources/medialib_tab_2/2.htm

EXTRACELLULARFLUID

Reception

Plasma membrane

Transduction

CYTOPLASM

Receptor

Signalmolecule

EXTRACELLULARFLUID

Reception

Plasma membrane

Transduction

CYTOPLASM

Receptor

Signalmolecule

Relay molecules in a signal transductionpathway

EXTRACELLULARFLUID

Reception

Plasma membrane

Transduction

CYTOPLASM

Receptor

Signalmolecule

Relay molecules in a signal transductionpathway

Response

Activationof cellularresponse

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

A conformational (shape) change in a receptor starts the process

Most signal receptors are plasma membrane proteins

Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors◦ Examples of hydrophobic messengers are the

steroid and thyroid hormones of animals An activated hormone-receptor complex can

act as a transcription factor, turning on specific genes

EXTRACELLULARFLUID

Plasmamembrane

The steroidhormone testosteronepasses through theplasma membrane.

Testosterone bindsto a receptor proteinin the cytoplasm,activating it.

The hormone-receptor complexenters the nucleusand binds to specificgenes.

The bound proteinstimulates thetranscription ofthe gene into mRNA.

The mRNA istranslated into aspecific protein.

CYTOPLASM

NUCLEUS

DNA

Hormone(testosterone)

Receptorprotein

Hormone-receptorcomplex

mRNA

New protein

https://www.youtube.com/watch?v=qOVkedxDqQo (bozeman signal transduction)

Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane

There are three main types of membrane receptors:1. G-protein-linked receptors2. Receptor tyrosine kinases3. Ion channel receptors

A G-protein-linked 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

Segment thatinteracts withG proteins

Signal-binding site

G-protein-linked receptor

Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines

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

Signalmolecule

Helix in themembrane

Signal-binding site

Tyr

Tyr

Tyr Tyr

Tyr

TyrTyrosines

Receptor tyrosinekinase proteins(inactive monomers)CYTOPLASM

Tyr

Tyr

Tyr Tyr

Tyr

Tyr Tyr

Tyr

Tyr Tyr

Tyr

Tyr

Tyr

Tyr

Tyr Tyr

Tyr

Tyr

Activated tyrosine-kinase regions(unphosphorylateddimer)

Signalmolecule

Dimer

Fully activated receptor tyrosine-kinase(phosphorylateddimer)

Tyr

Tyr

Tyr Tyr

Tyr

TyrPPP

PPPATP 6 ADP

Tyr

Tyr

Tyr Tyr

Tyr

TyrP

PP

PPP

Inactiverelay proteins

Cellularresponse 2

Cellularresponse 1

Activated relay proteins

6

An 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

Signalmolecule(ligand)

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate closed

Gate open

Cellularresponse

https://www.youtube.com/watch?v=_GraY9A8N4Q

Transduction usually involves multiple steps

Multistep pathways can amplify a signal: A few molecules can produce a large cellular response

The molecules that relay a signal from receptor are mostly proteins

Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated

In many pathways, the signal is transmitted by a cascade of protein phosphorylations

Turning activities on and off

Signal molecule

Activated relaymolecule

Receptor

Inactiveprotein kinase

1 Activeprotein kinase

1

Inactiveprotein kinase

2 Activeprotein kinase

2

Inactiveprotein kinase

3 Activeprotein kinase

3

ADP

Inactiveprotein

Activeprotein

Cellularresponse

Phosphorylation cascade

ATP

PPP i

ADPATP

PPP i

ADPATP

PPP i

P

P

P

Second messengers are small, nonprotein, water-soluble molecules or ions◦ The extracellular signal molecule that binds to the

membrane is a pathway’s “first messenger”◦ Second messengers can spread through cells by

diffusion◦ Second messengers are important in G-protein-

linked receptors and tyrosine kinases

• Cyclic AMP (cAMP) is one of the most widely used second messengers

• Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal

ATP Cyclic AMP AMP

Adenylyl cyclase

PyrophosphateP P i

Phosphodiesterase

H2O

Many signal molecules trigger formation of cAMP

cAMP

ATPSecondmessenger

First messenger(signal moleculesuch as epinephrine)

G-protein-linkedreceptor

G protein

Adenylylcyclase

Proteinkinase A

Cellular responses

GTP

Calcium ions (Ca2+) act as a second messenger in many pathways

Calcium is an important second messenger because cells can regulate its concentration

ATP

EXTRACELLULARFLUID

ATP

Mitochondrion

Ca2+

pump

Plasmamembrane

CYTOSOL

Endoplasmicreticulum (ER)

Ca2+

pump

Ca2+

pump

High [Ca2+]Key

Nucleus

Low [Ca2+]

CYTOSOL

Ca2+Endoplasmicreticulum (ER)

IP3-gatedcalcium channel

IP3 (secondmessenger)

DAG

PIP2G-protein-linkedreceptor Phospholipase C

G protein

Signal molecule(first messenger)

EXTRACELLULARFLUID

GTP

CYTOSOL

Ca2+Endoplasmicreticulum (ER)

IP3-gatedcalcium channel

IP3 (secondmessenger)

DAG

PIP2G-protein-linkedreceptor Phospholipase C

G protein

Signal molecule(first messenger)

EXTRACELLULARFLUID

GTP

Ca2+ (secondmessenger)

CYTOSOL

Ca2+Endoplasmicreticulum (ER)

IP3-gatedcalcium channel

IP3 (secondmessenger)

DAG

PIP2G-protein-linkedreceptor Phospholipase C

G protein

Signal molecule(first messenger)

EXTRACELLULARFLUID

GTP

Ca2+ (secondmessenger)

Variousproteinsactivated

Cellularre-sponses

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

Reception

Transduction

Inactive G protein

Active G protein (102 molecules)

Inactive adenylyl cyclase

Active adenylyl cyclase (102)

ATP

Cyclic AMP (104)

Inactive protein kinase A

Inactive phosphorylase kinase

Active protein kinase A (104)

Active phosphorylase kinase (105)

Active glycogen phosphorylase (106)

Inactive glycogen phosphorylase

Glycogen

Response

Glucose-1-phosphate(108 molecules)

GENE REGULATION:

Many other signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus

The final activated molecule may function as a transcription factor

ReceptionGrowth factor

Receptor

Phosphorylationcascade

Transduction

CYTOPLASM

Inactivetranscriptionfactor

Activetranscriptionfactor

PResponse

Gene

mRNA

DNA

NUCLEUS

Signalmolecule

Receptor

Relaymolecules

Response 1 Response 2 Response 3

Cell B. Pathway branches,leading to two responses

Cell A. Pathway leads to a single response

Cell C. Cross-talk occursbetween two pathways

Response 4 Response 5

Activationor inhibition

Cell D. Different receptorleads to a different response

LE 11-16

Signalmolecule

Plasmamembrane

Receptor

Scaffoldingprotein

Threedifferentproteinkinases

LE 11-16

Signalmolecule

Plasmamembrane

Receptor

Scaffoldingprotein

Threedifferentproteinkinases

Inactivation mechanisms are an essential aspect of cell signaling

When signal molecules leave the receptor, the receptor reverts to its inactive state

https://www.youtube.com/watch?v=D-usAds_-lU