Cell Communication

• Cell-to-cell communication is absolutely essential for multicellular organisms and is also important for many unicellular organisms

• Cells must communicate to coordinate their activities

Cell Communication

Biologists have discovered some universal mechanisms of cellular regulation, involving the same small set of cell-signaling mechanisms

The “Cellular Internet”

• External signals are converted into responses within the cell

Evolution of Cell Signaling

Yeast cells• Identify their mates by cell signaling

factorReceptor

Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type.

1

Mating. Binding of the factors to     receptors induces changes      in the cells that     lead to their     fusion.

New a/ cell. The nucleus of the fused cell includes all the genes from the a and cells.

2

3

factorYeast cell,mating type a

Yeast cell,mating type

a/

a

a

Methods used by Cells to Communicate

Cell-Cell communication

Cell Signaling using chemical messengers

Plasma membranes

Plasmodesmatabetween plant cells

Gap junctionsbetween animal cells

Local regulator diffuses through extracellular fluid

Target cell

Secretoryvesicle

Electrical signalalong nerve celltriggers release ofneurotransmitter

Neurotransmitter diffuses acrosssynapse

Target cellis stimulated

Local signaling

1. Local signaling over short distances

2. Long distance signaling

• Cell-Cell Recognition

• Local regulators

Paracrine (growth factors)

Synaptic (neurotransmitters)

• Hormones

Cell-Cell Communication

Plasma membranes

Plasmodesmatabetween plant cells

Gap junctionsbetween animal cells

Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.

Animal and plant cells

• Have cell junctions that directly connect the cytoplasm of adjacent cells

Cell-Cell Communication

Animal cells use gap junctions to send signals

• cells must be in direct contact

• protein channels connecting two adjoining cells

Gap junctionsbetween animal cells

Cell-Cell Communication

Plant cells use plasmodesmata to send signals

• cells must be in direct contact

• gaps in the cell wall connecting the two adjoining cells together

Plasmodesmata between plant cells

Local Signaling: Cell-Cell Recognition

In local signaling, animal cells may communicate via direct contact

• Membrane bound cell surface molecules

• Glycoproteins

• Glyolipids

(Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

Local Signaling: Local Regulators

In other cases, animal cells

• Communicate using local regulators

• Only work over a short distance

(a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid.

(b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.

Local regulator diffuses through extracellular fluid

Target cell

Secretoryvesicle

Electrical signalalong nerve celltriggers release ofneurotransmitter

Neurotransmitter diffuses acrosssynapse

Target cellis stimulated

Local signaling

Long-distance Signaling: Hormones

In long-distance signaling

• Both plants and animals use hormones

Hormone travelsin bloodstreamto target cells

(c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells.

Long-distance signaling

Bloodvessel

Targetcell

Endocrine cell

Long-Distance Signaling

Nervous System in Animals Electrical signals through neurons

Endocrine System in Animals Uses hormones to transmit messages

over long distances

Plants also use hormones Some transported through vascular

system Others are released into the air

How do Cells Communicate?

Earl W. Sutherland

• Discovered how the hormone epinephrine acts on cells

How do Cells Communicate?

Sutherland suggested that cells receiving signals went through three processes

Reception

Transduction

Response

Called Signal transduction pathways

• Convert signals on a cell’s surface into cellular responses

• Are similar in microbes and mammals, suggesting an early origin

How do Cells Communicate?

The process must involve three stages

1. Reception - a chemical signal binds to a cellular protein, typically at the cell’s surface

2. Transduction - binding leads to a change in the receptor that triggers a series of changes along a signal-transduction pathway

3. Response - the transduced signal triggers a specific cellular response

Signal Transduction Animation

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• http://www.wiley.com/legacy/college/boyer/0470003790/animations/signal_transduction/signal_transduction.htm

Signal molecules and Receptor Proteins

A cell targeted by a particular chemical signal has a receptor protein that recognizes the signal molecule

• recognition occurs when the signal binds to a specific site on the receptor because it is complementary in shape

When ligands (small molecules that bind specifically to a larger molecule) attach to the receptor protein, the receptor typically undergoes a change in shape

• this may activate the receptor so that it can interact with other molecules

Signal Molecules

• most signal molecules are water-soluble and too large to pass through the plasma membrane

• they influence cell activities by binding to receptor proteins on the plasma membrane

– binding leads to change in the shape of the receptor

– these trigger changes in the intracellular environment

There are three common types of membrane receptor proteins:

• G-protein coupled receptors• Receptor tyrosine-kinases• Ion channel receptors

1. ReceptionA signal molecule, a ligand, binds to a receptor

protein in a lock and key fashion, causing the receptor to change shape.

• Most receptor proteins are in the cell membrane but some are inside the cell.

G Protein- Coupled Receptor

• the receptor consists of seven alpha helices spanning the membrane

G protein-coupledreceptor

Plasmamembrane

Enzyme

G protein(inactive)

GDP

CYTOPLASM

Activatedenzyme

GTP

Cellular response

GDP

P

i

Activatedreceptor

GDP GTP

Signaling molecule

Inactiveenzyme

1 2

3 4

G-Protein Receptors

• effective signal molecules include yeast mating factors, epinephrine, other hormones, and neurotransmitters

Several human diseases are the results of activities, including bacterial infections, that interfere with G protein function

cholera

pertussis

botulism

Receptor tyrosine kinases

Signalmolecule

Signal-binding site

CYTOPLASM

Tyrosines

Signal moleculeHelix in the

Membrane

Tyr

TyrTyr

Tyr

Tyr

TyrTyr

TyrTyr

Tyr

Tyr

Tyr

Tyr

TyrTyr

Tyr

Tyr

Tyr Tyr

TyrTyr

Tyr

Tyr

Tyr

Tyr

TyrTyr

Tyr

Tyr

Tyr

DimerReceptor tyrosinekinase proteins(inactive monomers)

PP

PP

P

P Tyr

TyrTyr

Tyr

Tyr

TyrP

P

P

P

P

PCellularresponse 1

Inactiverelay proteins

Activatedrelay proteins

Cellularresponse 2

Activated tyrosine-kinase regions(unphosphorylateddimer)

Fully activated receptortyrosine-kinase(phosphorylateddimer)

6 ATP 6 ADP

Ligand-gated Ion Channels• Ligand-gated ion channels are

protein pores that open or close in response to a chemical signal

• this allows or blocks ion flow, such as Na+ or Ca2+

• binding by a ligand to the extracellular side changes the protein’s shape and opens the channel

• ion flow changes the concentration inside the cell

Signalingmolecule(ligand)

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed

1

2

3

Ion Channel Receptors

• Very important in the nervous system

• Signal triggers the opening of an ion channel– Depolarization– Triggered by

neurotransmitters

2. Transduction• Transduction: Cascades of molecular

interactions relay signals from receptors to target molecules in the cell

• Multistep pathways– Can amplify a signal (Amplifies the signal by

activating multiple copies of the next component in the pathway)

– Provide more opportunities for coordination and regulation

• At each step in a pathway, the signal is transduced into a different form, commonly a conformational change in a protein.

Signaling molecule

ReceptorActivated relaymolecule

Inactiveprotein kinase1 Active

proteinkinase1

Inactiveprotein kinase2

ATPADP Active

proteinkinase2

P

PPP

Inactiveprotein kinase3

ATPADP Active

proteinkinase3

P

PPP

i

ATPADP P

ActiveproteinPP

P i

Inactiveprotein

Cellularresponse

Phosphorylation cascade

i

Transduction:A Phosphorylation Cascade

Protein Phosphorylation and Dephosphorylation

Many signal pathways

• Include phosphorylation cascades

• In this process, a series of protein kinases add a phosphate to the next one in line, activating it

• Phosphatase enzymes then remove the phosphates

Signal molecule

Activeproteinkinase1

Activeproteinkinase2

Activeproteinkinase3

Inactiveprotein kinase1

Inactiveprotein kinase2

Inactiveprotein kinase3

Inactiveprotein

Activeprotein

Cellularresponse

Receptor

P

P

P

ATPADP

ADP

ADP

ATP

ATP

PP

PP

PP

Activated relaymolecule

i

Phosphorylation cascade

P

P

i

i

P

A phosphorylation cascade

A relay moleculeactivates protein kinase 1.1

2 Active protein kinase 1transfers a phosphate from ATPto an inactive molecule ofprotein kinase 2, thus activatingthis second kinase.

Active protein kinase 2then catalyzes the phos-phorylation (and activation) ofprotein kinase 3.

3

Finally, active proteinkinase 3 phosphorylates aprotein (pink) that brings about the cell’s response tothe signal.

4 Enzymes called proteinphosphatases (PP)catalyze the removal ofthe phosphate groupsfrom the proteins, making them inactiveand available for reuse.

5

The transduction stage of signaling is often a multistep process that amplifies the signal.

• About 1% of our genes are thought to code for kinases.

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Small Molecules and Ions as Second Messengers

Secondary messengers

• Are small, nonprotein, water-soluble molecules or ions

Cyclic AMP

• Many G-proteins trigger the formation of cAMP, which then acts as a second messenger in cellular pathways.

ATP

GTP

cAMP

Proteinkinase A

Cellular responses

G-protein-linkedreceptor

AdenylylcyclaseG protein

First messenger(signal moleculesuch as epinephrine)

Cyclic AMP

Cyclic AMP (cAMP)

• Is made from ATP

O–O O

O

N

O

O

O

O

P P P

PP P

O

O

O

O

O

OH

CH2

NH2 NH2 NH2

N

N

N

N

N

N

N

N

N

N

NO

O

O

ATP

Ch2 CH2

O

OH OH

P

O O

H2O

HOAdenylyl cyclase Phoshodiesterase

Pyrophosphate

Cyclic AMP AMPOH OH

O

i

3. Response

• Many possible outcomes

• This example shows a transcription response

Growth factor

Receptor

Phosphorylationcascade

Reception

Transduction

Activetranscriptionfactor Response

P

Inactivetranscriptionfactor

CYTOPLASM

DNA

NUCLEUSmRNA

Gene

• Specificity of the signal

– The same signal molecule can trigger different responses

– Many responses can come from one signal!

Signalingmolecule

Receptor

Relaymolecules

Response 1

Cell A. Pathway leadsto a single response.

Cell B. Pathway branches,leading to two responses.

Response 2 Response 3

• The signal can also trigger an activator or inhibitor

• The signal can also trigger multiple receptors and different responses

Response 4 Response 5

Activationor inhibition

Cell C. Cross-talk occursbetween two pathways.

Cell D. Different receptorleads to a different response.

Response- cell signaling leads to regulation of transcription (turn genes on or off) or cytoplasmic activities.

Long-distance Signaling - Intracellular signaling includes hormones that are hydrophobic and can cross the cell membrane.

Once inside the cell, the hormone attaches to a protein that takes it into the nucleus where transcription can be stimulated.

Testosterone acts as a transcription factor.

Hormone(testosterone)

EXTRACELLULARFLUID

Receptorprotein

DNA

mRNA

NUCLEUS

CYTOPLASM

Plasmamembrane

Hormone-receptorcomplex

New protein

• Steroid hormones– Bind to intracellular receptors

1 The steroid hormone testosterone passes through the plasma membrane.

The bound proteinstimulates thetranscription ofthe gene into mRNA.

4

The mRNA istranslated into aspecific protein.

5

Testosterone bindsto a receptor proteinin the cytoplasm,activating it.

2

The hormone-receptor complexenters the nucleusand binds to specific genes.

3

Signaling Efficiency: Scaffolding Proteins and Signaling

Complexes• Scaffolding proteins

– Can increase the signal transduction efficiency

Signalmolecule

Receptor

Scaffoldingprotein

Threedifferentproteinkinases

Plasmamembrane

Termination of the Signal

• Signal response is terminated quickly– By the reversal of ligand binding