Cell Communication

Cell Signaling

• Cell-to-cell communication is essential for multicellular organisms

• Communicate by chemical messengers• Animal and plant cells have cell junctions that

directly connect the cytoplasm of 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

• Local- paracrine, synaptic signaling• Long-distance- hormonal signaling (endocrine)

Signaling

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

The Three Stages of Cell Signaling

• Reception• Transduction• Response

Reception• The binding between a signal molecule (ligand) and

receptor is highly specific• A conformational change in a receptor is often the

initial transduction of the signal• Most signal receptors are plasma membrane proteins

EXTRACELLULARFLUID

Reception

Plasma membrane

Transduction

CYTOPLASM

Receptor

Signalmolecule

EXTRACELLULARFLUID

Reception

Plasma membrane

Transduction

CYTOPLASM

Receptor

Signalmolecule

Relay molecules in a signal transductionpathway

Transduction•Usually involves multiple steps•Multistep pathways can amplify a signal

EXTRACELLULARFLUID

Reception

Plasma membrane

Transduction

CYTOPLASM

Receptor

Signalmolecule

Relay molecules in a signal transductionpathway

Response

Activationof cellularresponse

ResponseSignal transduction pathways lead to regulation of one or more cellular activities

Intracellular Receptors• Some receptor proteins are intracellular, found

in the cytosol or nucleus of target cells• Small or hydrophobic chemical messengers

(lipid steroids) can readily cross the membrane and activate receptors

• 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

Receptors in the Plasma Membrane

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

• There are three main types of membrane receptors:– G-protein-linked receptors– Receptor tyrosine kinases– 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: • GTP= active GDP= inactive

Segment thatinteracts withG proteins

Signal-binding site

G-Protein-Linked Receptor

cAMP

ATPSecondmessenger

First messenger(signal moleculesuch as epinephrine)

G-protein-linkedreceptor

G protein

Adenylylcyclase

Proteinkinase A

Cellular responses

GTP

• Acts as a gate when the receptor changes shape

Ion Channel Receptor Signalmolecule(ligand)

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate closed

Gate open

Cellularresponse

Signal Transduction Pathways• The molecules that relay a signal from receptor

to response are mostly proteins• Behave similar to falling dominos• At each step, the signal is transduced into a

different form, usually a conformational change

EXTRACELLULARFLUID

Reception

Plasma membrane

Transduction

CYTOPLASM

Receptor

Signalmolecule

Relay molecules in a signal transductionpathway

Response

Activationof cellularresponse

Protein Phosphorylation and Dephosphorylation

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

• Phosphatase enzymes remove the phosphates• This phosphorylation and dephosphorylation

system acts as a molecular switch, 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

Small Molecules and Ions as Second Messengers

• 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 readily spread throughout cells by diffusion

• Second messengers participate in pathways initiated by G-protein-linked receptors and receptor tyrosine kinases

Cyclic AMP• 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

cAMP

ATPSecondmessenger

First messenger(signal moleculesuch as epinephrine)

G-protein-linkedreceptor

G protein

Adenylylcyclase

Proteinkinase A

Cellular responses

GTP

Cytoplasmic and Nuclear Responses

• Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities

• The response may occur in the cytoplasm or may involve action in the nucleus

• Many pathways regulate the activity of enzymes

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)

Note the amplification

• 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

Cytoplasmic and Nuclear Responses

ReceptionGrowth factor

Receptor

Phosphorylationcascade

Transduction

CYTOPLASM

Inactivetranscriptionfactor

Activetranscriptionfactor

PResponse

Gene

mRNA

DNA

NUCLEUS