What’s happeningWhat’s happening?. Symphony of communication

What’s happening?

http://www.youtube.com/watch?v=t80sdBtB-Gc

Symphony of communication

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LECTURE PRESENTATIONSFor CAMPBELL BIOLOGY, NINTH EDITION

Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson

© 2011 Pearson Education, Inc.

Lectures byErin Barley

Kathleen Fitzpatrick

Cell Communication

Chapter 11

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


Cellular communication

Types of signaling Contact

Local

Paracrine Synaptic

Long-distance

Endocrine system: via hormones

Neuronal: via elctricity



Local

Paracrine Synaptic

Long-distance





Local

Paracrine Synaptic

Long-distance





Local

Paracrine Synaptic

Long-distance


Neuronal: via electricity

Figure 11.1

• Concept 11.1: External signals are converted to responses within the cell

• Concept 11.2: Reception: A signaling molecule binds to a receptor protein, causing it to change shape

• Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cellConcept

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

• Concept 11.5: Apoptosis integrates multiple cell-signaling pathways

Concept 11.1: External signals are converted to responses within the cell

• 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

• Cells of different mating types locate each other via secreted factors specific to each type

• 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

• Signal transduction pathways convert signals on a cell’s surface into cellular responses


Communication between mating yeast cells

How canthis beanalogized

to people?

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/

• How could we find out how long ago cell communication evolved?


• How could we find out how long ago cell communication evolved?

• See if similar mechanisms are present in bacteria and recently developed organisms like people.


Individualrod-shapedcells

Spore-formingstructure(fruiting body)

Aggregation in progress

Fruiting bodies

1

2

3

0.5 mm

2.5 mm

The concentration of signaling molecules allows bacteria to sense local population density

Local and Long-Distance Signaling

• Cells in a multicellular organism 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

Figure 11.5a

Local signaling

Target cell

Secretingcell

Secretoryvesicle

Local regulatordiffuses throughextracellular fluid.

(a) Paracrine signaling using local regulators(b) Synaptic signaling with neurotransmitters

Electrical signalalong nerve celltriggers release ofneurotransmitter.

Neurotransmitter diffuses across synapse.

Target cellis stimulated.

Figure 11.5b

Long-distance signaling

Endocrine cell Bloodvessel

Hormone travelsin bloodstream.

Target cellspecificallybinds hormone.

(c) Endocrine (hormonal) signaling

The Three Stages of Cell Signaling:

1. Reception

2. Transduction

3. Response



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

Figure 11.6-1

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception

Receptor

Signalingmolecule

1

Figure 11.6-2

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception Transduction

Receptor

Signalingmolecule

Relay molecules in a signal transductionpathway

21

Figure 11.6-3

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception Transduction Response

Receptor

Signalingmolecule

Activationof cellularresponse

Relay molecules in a signal transductionpathway

321

Concept 11.2: Reception: A signaling molecule binds to a receptor protein, causing it to change shape


Receptors in the Plasma Membrane

• There are three main types of membrane receptors

1. G protein-coupled receptors

2. Receptor tyrosine kinases

3. Ion channel receptors


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

Figure 11.7b

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

Note: the enzyme is activated by shape change

Figure 11.8: The sturcutre of a G Protien-Coupled Receptor

Plasmamembrane

Cholesterol

2-adrenergicreceptors

Moleculeresemblingligand

2. Receptor tyrosine kinase

Signalingmolecule (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

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

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

• Tidbit: Abnormal functioning of RTKs is associated with many types of cancers


Figure 11.7d

Signalingmolecule (ligand)

21 3

Gate closed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed

A ligand-gated ion channel receptor acts as a gate when the receptor changes shapeWhen a ligand binds to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

Intracellular Receptors

• 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

– Examples of hydrophobic messengers are the steroid and thyroid (lipid soluble) hormones of animals


Figure 11.9-1Hormone(testosterone)

Receptorprotein

Plasmamembrane

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID


Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID


Receptorprotein

Plasmamembrane


DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID


Receptorprotein

Plasmamembrane


DNA

mRNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID


Receptorprotein

Plasmamembrane

EXTRACELLULARFLUID


DNA

mRNA

NUCLEUS

CYTOPLASM

New protein

Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell

• Signal transduction usually involves multiple steps– What are some benefits of a multistep pathway

a.k.a. cascade?


Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell

• Signal transduction usually involves multiple steps, a.k.a. cascade?– Benefit 1: can amplify a signal: (A few molecules

can produce a large cellular response)

– Benefit 2: provide more opportunities for coordination and regulation of the cellular response


Protein Phosphorylation and Dephosphorylation is the cascade’s signal

• Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation

• Protein phosphatases remove the phosphates from proteins, a process called 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

Activeprotein kinase

3


2


3

Inactiveprotein

Activeprotein

Cellularresponse

ATPADP

ATPADP

ATPADP

PP

PP

PP

P

P

P

P i

P i

P i

Figure 11.10

“upstream”/”downstream” regulation

Small Molecules and Ions as Second Messengers

• 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– Cyclic AMP and calcium ions are common second

messengers


Figure 11.11

Adenylyl cyclase Phosphodiesterase

Pyrophosphate

AMP

H2O

ATP

P iP

cAMP

What other organic molecule do cAMP resemble?

Why?

Figure 11.12

G protein

First messenger(signaling moleculesuch as epinephrine)


Adenylylcyclase

Second messenger

Cellular responses

Proteinkinase A

GTP

ATP

cAMP

Calcium Ions and Inositol Triphosphate (IP3)

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

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


Figure 11.13

Mitochondrion

EXTRACELLULARFLUID

Plasmamembrane

Ca2

pump

Nucleus

CYTOSOL

Ca2

pump

Ca2

pump

Endoplasmicreticulum(ER)

ATP

ATP

Low [Ca2 ]High [Ca2 ]Key


Animation: Signal Transduction Pathways Right-click slide / select “Play”

G protein

EXTRA-CELLULARFLUID

Signaling molecule(first messenger)


Phospholipase C

DAG

PIP2

IP3

(second messenger)

IP3-gatedcalcium channel

Endoplasmicreticulum (ER)

CYTOSOL

Ca2

GTP

Figure 11.14-1: Calcium and IP3 in signaling pathways

Figure 11.14-2

G protein

EXTRA-CELLULARFLUID



Phospholipase C

DAG

PIP2

IP3

(second messenger)



CYTOSOL

Ca2

(secondmessenger)

Ca2

GTP

Figure 11.14-3

G protein

EXTRA-CELLULARFLUID



Phospholipase C

DAG

PIP2

IP3

(second messenger)



CYTOSOL

Variousproteinsactivated

Cellularresponses

Ca2

(secondmessenger)

Ca2

GTP

Concept 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities• The final activated molecule in the signaling

pathway may have a response in the cytoplasm (e.g. changing shape of cytoskeleton or regulating enzymes) or function as a transcription factor


Figure 11.15Growth factor

Receptor

Reception

Transduction

CYTOPLASM

Response

Inactivetranscriptionfactor

Activetranscriptionfactor

DNA

NUCLEUS mRNA

Gene

Phosphorylationcascade

P

Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine.

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)

• Signaling pathways can also affect the overall behavior of a cell, for example, changes in cell shape


Wild type yeast (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.

RESULTS

CONCLUSION

What is this showing?

Figure 11.17a

Wild type (with shmoos)

Fine-Tuning of the Response

• There are four aspects of fine-tuning to consider:1. Amplification of the signal (and thus the

response)

2. Specificity of the response

3. Overall efficiency of response, enhanced by scaffolding proteins

4. Termination of the signal


Signal Amplification

• Enzyme cascades amplify the cell’s response• At each step, the number of activated products is

much greater than in the preceding step


Figure 11.18 The specificity of cell signaling.

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.

Figure 11.19

Signalingmolecule

Receptor

Plasmamembrane

Scaffoldingprotein

Threedifferentproteinkinases

Signaling Efficiency: Scaffolding Proteins and Signaling Complexes

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


Concept 11.5: Apoptosis integrates multiple cell-signaling pathways

• Apoptosis is programmed or controlled cell suicide

• WHY IS THIS FUNCTION CRITICAL?


Concept 11.5: Apoptosis integrates multiple cell-signaling pathways

• Apoptosis is programmed or controlled cell suicide

• Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells

• Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells


Figure 11.20: white blood cell apoptosis

2 m

Apoptosis in the Soil Worm Caenorhabditis elegans

• Apoptosis is important in shaping an organism during embryonic development

• The role of apoptosis in embryonic development was studied in Caenorhabditis elegans

• In C. elegans, apoptosis results when proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis


Figure 11.21

Mitochondrion

Ced-9protein (active)inhibits Ced-4activity

Receptorfor death-signalingmolecule

Ced-4 Ced-3

Inactive proteins

(a) No death signal

Death-signalingmolecule

Ced-9(inactive)

Cellformsblebs

ActiveCed-4

ActiveCed-3

Otherproteases

NucleasesActivationcascade

(b) Death signal

Apoptotic Pathways and the Signals That Trigger Them

• Caspases are the main proteases (what are these?) that carry out apoptosis

• Apoptosis can be triggered by– An extracellular death-signaling ligand – DNA damage in the nucleus– Protein misfolding in the endoplasmic reticulum


• Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers


Figure 11.22: apoptosis in paw development of the mouse

Interdigital tissueCells undergoing

apoptosisSpace between

digits1 mm

REVIEW

Reception1 2 3Transduction Response

Receptor

Signalingmolecule

Relay molecules

Activation of cellularresponse

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