cell communication chapter 11 cell communication

Cell Communication

Chapter 11Cell Communication

Overview: Cellular Messaging

Cell-to-cell communication is essential for both multicellular and unicellular organisms

Biologists have discovered some universal mechanisms of cellular regulation

Cells most often communicate with each other via chemical signals

For example, the fight-or-flight response is triggered by a signaling molecule called epinephrine

Cells Recognize and Respond to External Signals

Microbes provide a glimpse of the role of cell signaling in the evolution of life

Evolution of Cell Signaling

The yeast, Saccharomyces cerevisiae, has two mating types, a and

different mating types locate each other via secreted factors

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

Exchange of mating factors

Receptor factor

a factorYeast cell,

mating type aYeast cell,

mating type

Mating

New a/ cell

1

2

3

a

a

a/

Individualrod-shapedcells

Spore-formingstructure(fruiting body)

Aggregation in progress

Fruiting bodies

1

2

3

0.5 mm

2.5 mm

Communication in Bacteria: Cell Signaling

Quorum sensing to signal other cells to gather!

Signaling in Multiceullar Organisms: “Local Signaling”

Multicellular organism’s cells 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, or cell-cell recognition

Figure 11.4Plasma membranes

Gap junctionsbetween animal cells

Plasmodesmatabetween plant cells

(a) Cell junctions

(b) Cell-cell recognition

In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances

The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal

Local Signaling

Local signaling

Target cell

Secretingcell

Secretoryvesicle

Local regulatordiffuses throughextracellular fluid.

(a) Paracrine signaling (b) Synaptic signaling

Electrical signalalong nerve celltriggers release ofneurotransmitter.

Neurotransmitter diffuses across synapse.

Target cellis stimulated.

Local Regulators: work over very short distances

Long Distance Signaling

Long-distance signaling

Endocrine cell Bloodvessel

Hormone travelsin bloodstream.

Target cellspecificallybinds hormone.

(c) Endocrine (hormonal) signaling

• Hormones are used in long-distance signaling.

• Both plants and animals have hormones!

• AKA endocrine signaling

The Three Stages of Cell Signaling: A Preview

Earl W. Sutherland discovered how the hormone epinephrine acts on cells

Sutherland suggested that cells receiving signals went through three processes

Reception Transduction Response

© 2011 Pearson Education, Inc.

Animation: Overview of Cell Signaling Right-click slide / select “Play”

Reception: A cell recognizes the signal!

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception

Receptor

Signalingmolecule

1

What determines if a cell will respond to a signal?

Transduction: Converting the Signal to Action

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception Transduction

Receptor

Signalingmolecule

Relay molecules in a signal transductionpathway

21

Response: Specific Cellular Action

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception Transduction Response

Receptor

Signalingmolecule

Activationof cellularresponse

Relay molecules in a signal transductionpathway

321

Reception: Signaling molecule and Receptor ProteinsThe binding between a signal molecule (ligand) and receptor is highly specific

Receptors in the Plasma Membrane

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

There are three main types of membrane receptors G protein-coupled receptors Receptor tyrosine kinases Ion channel receptors

Type 1: G-protein Coupled Receptors

G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors

Work 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

G protein-coupled receptor

Signaling molecule binding site

Segment thatinteracts with G proteins

G-protein Function: “On” and “Off”

G protein-coupledreceptor

21

3 4

Plasmamembrane

G protein(inactive)

CYTOPLASM Enzyme

Activatedreceptor

Signalingmolecule

Inactiveenzyme

Activatedenzyme

Cellular response

GDPGTP

GDPGTP

GTP

P i

GDP

GDP

Energy source GTP turns on the G proteinGDP turns it off

Receptor Tyrosine Kinases Receptor tyrosine

kinases (RTKs) are membrane receptors that attach phosphates to tyrosines

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

Active form is a dimer

Abnormal functioning of RTKs is associated with many types of cancers

RTK – Activation Through DimerizationSignalingmolecule (ligand)

21

3 4

Ligand-binding site

helix in themembrane

Tyrosines

CYTOPLASM Receptor tyrosinekinase proteins(inactive monomers)

Signalingmolecule

Dimer

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P

P

P

P

P

P

P

P

P

P

P

P

Activated tyrosinekinase regions(unphosphorylateddimer)

Fully activatedreceptor tyrosinekinase(phosphorylateddimer)

Activated relayproteins

Cellularresponse 1

Cellularresponse 2

Inactiverelay proteins

6 ATP 6 ADP

Ligand-Gated Ion Channels

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

Ligand-Gated Ion Channel Activation

Signalingmolecule (ligand)

21 3

Gate closed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed

Signaling molecule binds to allow specific ions into cellThese ions produce cellular responses (Ca+2 one of the most important!)

Intracellular Receptors: Hormones

Intracellular receptor proteins are found in the cytosol or nucleus of target cells

Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors

steroid and thyroid hormones of animals

Can act as a transcription factor, turning on specific genes

Hormone ActivationHormone(testosterone)

Receptorprotein

Plasmamembrane

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

The signaling molecule is permeable to the membrane

The receptor is found inside the cell

Figure 11.9-2 Hormone(testosterone)

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUIDHormone Activation

Hormone and receptor bond, activating the complex

Figure 11.9-3Hormone(testosterone)

Receptorprotein

Plasmamembrane


DNA

NUCLEUS

CYTOPLASM


One possible function of these complexes are to initiate the synthesis of specific genes

Here the complex enters the nucleus , acting as a transcription factor


Receptorprotein

Plasmamembrane


DNA

mRNA

NUCLEUS

CYTOPLASM


The target RNA is made and exported for protein production


Receptorprotein

Plasmamembrane

EXTRACELLULARFLUID


DNA

mRNA

NUCLEUS

CYTOPLASM

New protein

Hormone Activation

Target protein is synthesized, completing the initial signal’s response

Transduction: Signal Transduction Cascades relay signals from receptors to target molecules in the cell

Multistep pathways can amplify a signal and provide more opportunities for coordination and regulation of the cellular response

Signal Transduction Pathways

Proteins in the cytosol relay a signal from receptor

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

At each step, the signal is transduced into a different form, usually a shape change in a protein

One of the most common methods of regulating the signal is through phosphorylation and dephosphorylation

Protein Phosphorylation and Dephosphorylation: Molecular Switches

Protein kinases transfer phosphates from ATP to protein phosphorylation

Protein phosphatases remove the phosphates dephosphorylation

This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off or up or down, as required

Receptor

Signaling molecule

Activated relaymolecule

Phosphorylation cascade

Inactiveprotein kinase

1 Activeprotein kinase

1

Activeprotein kinase

2


3


2


3

Inactiveprotein

Activeprotein

Cellularresponse

ATPADP

ATPADP

ATPADP

PP

PP

PP

P

P

P

P i

P i

P i

Activated relaymolecule

Phosphorylation cascade


1 Activeprotein kinase

1


2


3


2


3

Inactiveprotein

Activeprotein

ATPADP

ATPADP

ATPADP

PP

PP

PP

P

P

P i

P i

P i

P

Secondary Messengers: Small Molecules and Ions

The extracellular signal molecule (ligand) that binds to the receptor is a pathway’s “first messenger”

Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion

Second messengers participate in pathways initiated by GPCRs and RTKs

Cyclic AMP and calcium ions are common second messengers

Cyclic AMP: Activation• ATP is made into cAMP in response to an extracellular signal

Adenylyl cyclase

Pyrophosphate

ATP

P iP

cAMP

Cyclic AMP: Regulation

Phosphodiesterase

AMP

H2O

cAMP

H2O

cAMP Pathway

Many signal molecules trigger formation of cAMP

cAMP usually activates protein kinase A, which phosphorylates various other proteins

Regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase

G protein

First messenger(signaling moleculesuch as epinephrine)


Adenylylcyclase

Second messenger

Cellular responses

Proteinkinase A

GTP

ATP

cAMP

Calcium Ions

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

Cells can regulate its concentration

A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol

Mitochondrion

EXTRACELLULARFLUID

Plasmamembrane

Ca2

pump

Nucleus

CYTOSOL

Ca2

pump

Ca2

pump

Endoplasmicreticulum(ER)

ATP

ATP

Low [Ca2 ]High [Ca2 ]Key

Calcium and Inositol Triphosphate

Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers

G protein

EXTRA-CELLULARFLUID

Signaling molecule(first messenger)


Phospholipase C

DAG

PIP2

IP3

(second messenger)

IP3-gatedcalcium channel

Endoplasmicreticulum (ER)

CYTOSOL

Ca2

GTP

G protein

EXTRA-CELLULARFLUID



Phospholipase C

DAG

PIP2

IP3

(second messenger)



CYTOSOL

Ca2

(secondmessenger)

Ca2

GTP

G protein

EXTRA-CELLULARFLUID



Phospholipase C

DAG

PIP2

IP3

(second messenger)



CYTOSOL

Variousproteinsactivated

Cellularresponses

Ca2

(secondmessenger)

Ca2

GTP

Response: Cell signaling leads to regulation of transcription or cytoplasmic activities

•The cell’s response to an extracellular signal is sometimes called the “output response”

Nuclear and Cytoplasmic Responses

Signal transduction pathways lead to regulation of cellular activities

The response can be cytoplasm or in the nucleus

Regulate synthesis of proteins, usually by turning genes on or off

Molecules may function as a transcription factor

Growth factor

Receptor

Reception

Transduction

CYTOPLASM

Response

Inactivetranscriptionfactor

Activetranscriptionfactor

DNA

NUCLEUS mRNA

Gene

Phosphorylationcascade

P

Wild type (with shmoos) Fus3 formin

Matingfactoractivatesreceptor.

Matingfactor G protein-coupled

receptor

Shmoo projectionforming

Formin

G protein binds GTPand becomes activated.

2

1

3

4

5

P

P

P

PForminFormin

Fus3

Fus3Fus3

GDPGTP

Phosphory- lation cascade

Microfilament

Actinsubunit

Phosphorylation cascadeactivates Fus3, which movesto plasma membrane.

Fus3 phos-phorylatesformin,activating it.

Formin initiates growth ofmicrofilaments that formthe shmoo projections.

CONCLUSION

Signals Can Regulate Overall Cell Behavior

Fine-Tuning of the Response

There are four aspects of fine-tuning to consider Amplification of the signal (and thus the response) Specificity of the response Overall efficiency of response, enhanced by scaffolding proteins Termination of the signal

Fine Tuning 1 Responses: Amplification of Signal

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)

Glycogen

Glucose 1-phosphate (108 molecules)

Enzyme cascades amplify the cell’s response

At each step, the number of activated products is much greater than in the preceding step

Fine Tuning 2: The Specificity of Cell Signaling and Coordination of the Response

Signalingmolecule

Receptor

Relay molecules

Response 1

Cell A. Pathway leadsto a single response.

Response 2 Response 3 Response 4 Response 5

Activationor inhibition

Cell B. Pathway branches,leading to two responses.

Cell C. Cross-talk occursbetween two pathways.

Cell D. Different receptorleads to a differentresponse.

Different kinds of cells have different collections of proteins

Respond to different signals

Same signal can have different effects in cells

Signalingmolecule

Receptor

Relay molecules

Response 1

Cell A. Pathway leadsto a single response.

Response 2 Response 3

Cell B. Pathway branches,leading to two responses.

Response 4 Response 5

Activationor inhibition

Cell C. Cross-talk occursbetween two pathways.

Cell D. Different receptorleads to a differentresponse.

Pathway branching and “cross-talk” further help the cell coordinate incoming signals

Fine Tuning 3:Signaling Efficiency: Scaffolding Proteins and Signaling Complexes

Scaffolding proteins are large relay proteins to which other relay proteins are attached and can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway

Signalingmolecule

Receptor

Plasmamembrane

Scaffoldingprotein

Threedifferentproteinkinases

Fine Tuning 4:Termination of the Signal

Inactivation mechanisms are an essential aspect of cell signaling

If ligand concentration falls, fewer receptors will be bound

Unbound receptors revert to an inactive state

Signal Review

Reception1 2 3Transduction Response

Receptor

Signalingmolecule

Relay molecules

Activation of cellularresponse