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CH11 Cell Communication

CH11 Cell Communication. VOCABULARY directions: mark each term to indicate if you know it, are unsure, or don’t. amplifycommunicationdeleterious elaborate

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CH11 Cell Communication

VOCABULARYdirections: mark each term to indicate if you know it, are unsure,

or don’t.

amplify communication deleterious elaborateembryology evolution fluid mosaic model mechanismphosphorylation prophylactic regulation responsesignaling signal molecule specify second

messengerssignal transduction quorum sensing IP3 G protein

QUESTIONS generate a list to be answered todayWho What Where When Which How Why

communication

You know it is important.What does it mean?Brainstorm words related to “communication”.

Where on the cell does the “communication” occur?

• “speaking” occurs through the production and release of LIGANDS hormones or other chemical messengers using the cells machinery, vesicles, and exocytosis.

• “Listening” occurs by receptor proteins embedded in the cell membrane and by way of signal transduction pathways (domino effect of sorts) .

• “Reacting” occurs when specific enzymes become activated (because of the signal transduction pathway) and the cell performs a specific function.

How do cells communicate?

They are a lot like you… they use many different methods for communicating and their “messages” can result in a variety of responses. Process info via SIGNAL TRANSDUCTION PATHWAY

COMMUNICATIONTalking, listening, & responding.

Cells communicate by generating, transmitting and receiving chemical signals.

Big Idea 3: Living systems store, retrieve, transmit and respond to information essential to life processes.

Big Idea 1: The process of evolution drives the diversity and unity of life.

The expression of genetic material controls cell products, and these products determine the metabolism and nature of the cell.

1) Gene expression is regulated by both – 1)environmental signals and – 2)developmental cascades or stages.

2) Cell signaling mechanisms can also modulate and control gene expression.

3) Structure and Function in biology involve two interacting aspects: – 1) the presence of necessary genetic information and – 2) the correct and timely expression of this information.

Cell communication processes share common features that reflect a shared evolutionary history.

• Communication involves transduction of stimulatory or inhibitory signals from other cells, organisms or the environment.

• Correct and appropriate signal transduction processes are generally under strong selective pressure.

• In single-celled organisms, signal transduction pathways influence how the cell responds to its environment.Examples:– Use of chemical messengers by microbes to communicate with other

nearby cells and to regulate specific pathways in response to population density (quorum sensing)

– Use of pheromones to trigger reproduction and developmental pathways

– Response to external signals by bacteria that influences cell movement

Figure 11.3

Individualrod-shapedcells

Spore-formingstructure(fruiting body)

Aggregation in progress

Fruiting bodies

1

2

3

0.5 mm

2.5 mm

Communication among bacteriaQUORUM SENSING- bacteriaCan sense changes in densityAnd act appropriately.

Figure 11.3a

Individual rod-shaped cells1

Figure 11.3b

Aggregation in progress2

Figure 11.3c

Spore-forming structure(fruiting body)

0.5 mm

3

Figure 11.3d

Fruiting bodies

2.5 mm

A variety of intercellular and intracellular signal transmissions mediate gene expression.

a. Signal transmission within and between cells mediates gene expression.b. EXAMPLES: • Cytokines regulate gene expression to allow for cell replication and

division.YEAST• Mating pheromones trigger mating gene expression in yeast.BACTERIA• Levels of cAMP regulate metabolic gene expression in bacteria.PLANTS• Ethylene (hormone) levels cause changes in the production of different

enzymes, allowing fruits to ripen.• Gibberellin (hormone) causes seed germination.ANIMALS• Expression of the SRY gene triggers the male sexual development pathway

in animals.

• Signals come from cells or changes in their physical environment: – Chemicals (pheromones, hormones)– Light electromagnetic radiation, touch, gravity

• Receptors are proteins embedded in the cell membrane.• Signal transduction pathways relay signals from

receptors to cellular responses.• Responses include: specific enzyme activation

– Inhibitory response (via inhibitors)– Excitatory response (via activators- coenzyme or cofactor)

Why do cells need to communicate?

• (unicellular) To be able to survive and reproduce – Find food and water– Escape/avoid danger– Find mates

• (multicellular) To develop from a fertilized egg.– Differentiation– Programmed cell death (Apoptosis)

Figure 11.22

Interdigital tissueCells undergoing

apoptosisSpace between

digits1 mm

Effect of apoptosis during paw development in the mouse.

Ex.Morphogens stimulate cell differentiation and development.

Figure 11.20

2 m

Apoptosis of a human white blood cell.

Once it engulfs bacteria it commits “cell suicide” by carefully packaging its contents into multiple vesicles (membrane bound bags).

Figure 11.1

How does cell signaling trigger the desperate flight of this gazelle?Have you ever been scared? What does your body do?

• The “fight or flight” response is signaled by the hormone epinepherine or adrenaline.

• Causes changes to maximize ATP production – the release of glucose from muscles and liver cells– Increase in respiration depth and rate– Increase in heart rate

Figure 11.16

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)

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

How is communication different btwn single and multicellular organisms?

• In single-celled organisms, signal transduction pathways influence how the cell responds to its environment.

whereas

• In multicellular organisms, signal transduction pathways coordinate the activities within individual cells that support the function of the organism as a whole.– Temperature determination of sex in some vertebrate organisms – DNA repair mechanisms– Epinephrine stimulation of glycogen breakdown in mammals

How is communication different in multicellular organisms?

• In multicellular organisms, cell-to-cell and environment-to-cell chemical signaling pathways direct complex processes.– Ex. cell and organ differentiation to whole organism physiological

responses and behaviors.

• Certain signal pathways involve direct cell-to-cell contact, operate over very short distances, and may be determined by the structure of the organism or organelle, including– plasmodesmata in plants and – receptor-to-recognition protein interaction in the vertebrate

immune system.

Figure 11.4Plasma membranes

Gap junctionsbetween animal cells

Plasmodesmatabetween plant cells

(a) Cell junctions

(b) Cell-cell recognition Communication by direct contact between cells.

Which life forms use cell communication?

• Cell-to-cell communication is ubiquitous in biological systems, from archaea and bacteria to multicellular organisms.

• The basic chemical processes by which cells communicate are shared across evolutionary lines of descent, and communication schemes are the products of evolution.

• For cells to function in a biological system, they must communicate with other cells and respond to their external environment.

When did cell communication evolve?

• Cell-to-cell communication is a component of higher-order biological organization and responses.

• Communication evolved billions of years ago among the most ancient bacteria.

OVERVIEW:

1) Cell communication evolved early in the history oflife.• Cell-to-cell communication is essential for multicellular

organisms. The trillions of cells in a human or an oak tree must communicate in order to develop from a fertilized egg.

• Additional evidence for the evolutionary relatedness of all life comes from discovering some universal mechanisms of cellular regulation.– Q: What molecular evidence suggests the unity of life on Earth

(descent from a common ancestor)?

• Knowledge of cell signaling mechanisms are answering questions in medicine and biology in these areas: embryological development, hormone action, cancer.– Ex. Changes in p53 activity can result in cancer.

• Examples of signals that can be received by cells and the possible responses:– Changes in light duration lead to changes in plants

(dropping leaves, flowering)– Light & phototropism (plant cell growth toward light)– Gravity or touch effects plant growth (shoots away from

gravity, roots toward gravity)

b. Signal transmission within and between cells mediates cell function.

• Main topic of cell “conversation” = SEX…• Ex. YEAST Saccharomyces cerevisiae• Mating pheromones in yeast trigger mating

genes expression and sexual reproduction. • Q: How is the mating signal at the yeast cell

surface “transduced”, or changed, into a form that brings about the cellular response of mating?

• A: Signal Transduction Pathway

Figure 11.2

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/

Communication between mating yeast cells.

2 mating types

Each secretesA mating factorThat binds to the otherCell.

• Scientists think signaling mechanisms evolved first in ancient prokaryotes and single celled eukaryotes and were then adopted for new uses by their multicellular descendants.

Figure 11.5

Local signaling Long-distance 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.

Endocrine cell Bloodvessel

Hormone travelsin bloodstream.

Target cellspecificallybinds hormone.

(c) Endocrine (hormonal) signaling

2) Communicating cells can be close together or far apart.

Local signaling: paracrine or synaptic involves…secreting molecules short distances. Ex. neurotransmitters.Long distance (hormonal) signaling… secretes hormones for signaling at greater distances. Known as ENDOCRINE signaling.

Local and long-distance cell signaling by secreted molecules in animals.

Figure 11.6-3

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception Transduction Response

Receptor

Signalingmolecule

Activationof cellularresponse

Relay molecules in a signal transductionpathway

321

3) The 3 stages of cell signaling:

#1 reception: ligand binding to receptor#2 transduction: relay molecules employed #3 response: activation of cellular response

THE DETAILS:

RECEPTION & THE INITIATION OF TRANSDUCTION

Signal transduction pathways link signal reception with cellular response.

• 1) Signaling begins with the recognition of a chemical messenger, a ligand, by a receptor protein.

• Different receptors recognize different chemical messengers, which can be – peptides, – small chemicals or – proteins, in a specific one-to-one relationship.

• 2) A receptor protein recognizes signal molecules, causing the receptor protein’s shape to change,

• which initiates transduction of the signal.

• Examples: – G-protein linked receptors– Receptor tyrosine kinases– Ligand-gated ion channels– The Exception: Non-membrane protein receptors

Figure 11.7a

G protein-coupled receptor

Signaling molecule binding site

Segment thatinteracts with G proteins

G-protein linked receptor

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

G-protein linked receptors

Explain in in your own words what is happening during steps 1-4.

Figure 11.7c

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 Explain steps 1-4 in your own words.

Figure 11.7d

Signalingmolecule (ligand)

21 3

Gate closed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed

LIGAND GATED ION CHANNELSExplain steps 1-3 in your own words.

Cellular response ex. Muscle Cell contractions.

Figure 11.9-1

Hormone(testosterone)

Receptorprotein

Plasmamembrane

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

The exceptions:Non membrane proteinReceptors

Are found in the cytoplasm.

are activated by Steroid hormones.

Activate transcription Factors in the nucleus.

Figure 11.9-2

Hormone(testosterone)

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUIDThe exceptions:

Non membrane proteinReceptors

Are found in the cytoplasm.

are activated by Steroid hormones.

Activate transcription Factors in the nucleus.

Why is is that steroidHormones can passThrough the cell membrane?

Figure 11.9-3

Hormone(testosterone)

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

The exceptions:Non membrane proteinReceptors

Are found in the cytoplasm.

are activated by Steroid hormones.

Activate transcription Factors in the nucleus.

And nuclear envelope?

Figure 11.9-4

Hormone(testosterone)

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

mRNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

The exceptions:Non membrane proteinReceptors

Are found in the cytoplasm.

are activated by Steroid hormones.

Activate transcription Factors in the nucleus.

Steroids are lipids.Like dissolves like.Are not repelled by theHydrophobic tails of thePhospholipid bilayer.

Figure 11.9-5

Hormone(testosterone)

Receptorprotein

Plasmamembrane

EXTRACELLULARFLUID

Hormone-receptorcomplex

DNA

mRNA

NUCLEUS

CYTOPLASM

New protein

The exceptions:Non membrane proteinReceptors

Are found in the cytoplasm.

are activated by Steroid hormones.

Activate transcription Factors in the nucleus.

SIGNAL TRANSDUCTION PATHWAYS

• 1) Signal transduction is the process by which a signal is converted to a cellular response.

CELLULAR RESPONSES TO SIGNALS

1) In response to a signal, a cell may regulate activities in the cytoplasm or transcription in the nucleus.

2) Elaborate pathways amplify and specify the cells response to signals.

• Signaling cascades relay signals from receptors to cell targets, often amplifying the incoming signals, with the result of appropriate responses by the cell.

• Second messengers are often essential to the function of the cascade.

• Examples of second messengers:– Cyclic AMP cAMP– inositol triphosphate IP3

Figure 11.11

Adenylyl cyclase Phosphodiesterase

Pyrophosphate

AMP

H2O

ATP

P iP

cAMP

Why is the molecule called “cyclic” AMP not just AMP?

Figure 11.12

G protein

First messenger(signaling moleculesuch as epinephrine)

G protein-coupledreceptor

Adenylylcyclase

Second messenger

Cellular responses

Proteinkinase A

GTP

ATP

cAMP

1st messenger?2nd messenger?

Figure 11.14-1

G protein

EXTRA-CELLULARFLUID

Signaling molecule(first messenger)

G protein-coupledreceptor

Phospholipase C

DAG

PIP2

IP3

(second messenger)

IP3-gatedcalcium channel

Endoplasmicreticulum (ER)

CYTOSOL

Ca2

GTP

What is the 1st messenger?What is the 2nd messenger?

Figure 11.14-2

G protein

EXTRA-CELLULARFLUID

Signaling molecule(first messenger)

G protein-coupledreceptor

Phospholipase C

DAG

PIP2

IP3

(second messenger)

IP3-gatedcalcium channel

Endoplasmicreticulum (ER)

CYTOSOL

Ca2

(secondmessenger)

Ca2

GTP

What is the “other” 2nd messenger?

Figure 11.14-3

G protein

EXTRA-CELLULARFLUID

Signaling molecule(first messenger)

G protein-coupledreceptor

Phospholipase C

DAG

PIP2

IP3

(second messenger)

IP3-gatedcalcium channel

Endoplasmicreticulum (ER)

CYTOSOL

Variousproteinsactivated

Cellularresponses

Ca2

(secondmessenger)

Ca2

GTP

= Amplified response

3) Major mechanisms of signal transduction pathways:

• Protein modifications (Methylation)– Epigenetic control of the genome changes the signaling

process.• Phosphorylation cascades in which a series of

protein kinases add a phosphate group to the next protein in the cascade sequence

4) Certain small molecules and ions are key components of signaling pathways.

Figure 11.15Growth factor

Receptor

Reception

Transduction

CYTOPLASM

Response

Inactivetranscriptionfactor

Activetranscriptionfactor

DNA

NUCLEUS mRNA

Gene

Phosphorylationcascade

P

Figure 11.10

Receptor

Signaling molecule

Activated relaymolecule

Phosphorylation cascade

Inactiveprotein kinase

1 Activeprotein kinase

1

Activeprotein kinase

2

Activeprotein kinase

3

Inactiveprotein kinase

2

Inactiveprotein kinase

3

Inactiveprotein

Activeprotein

Cellularresponse

ATPADP

ATPADP

ATPADP

PP

PP

PP

P

P

P

P i

P i

P i

Figure 11.17

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.

RESULTS

CONCLUSION

Figure 11.18

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.

Changes in signal transduction pathways can alter cellular response.

• 1) Conditions where signal transduction is blocked or defective can be deleterious, preventative, or prophylactic.

• Diseases: Diabetes, heart disease, neurological disease, autoimmune disease,

cancer, cholera Ex. Carcinogens can mutate the P53 (tumor supressor gene). The gene normally

codes for a protein that controls the cell cycle. • Effects of: Effects of neurotoxins, poisons, pesticidesEx. Neurotoxin BOTOX blocks the neurotransmitter acetyl choline from binding to

muscle cells so it induces paralysis. • Drugs: Hypertensives, Anesthetics, Antihistamines and Birth Control Drugs

QUIZ

Signal Overview

Indicate where each of the labels should appear in the figure.

• Receptor• Relay molecules• Transduction• Activation of cellular response

• Signaling molecule• Response• Reception

Figure 11.6-3

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception Transduction Response

Receptor

Signalingmolecule

Activationof cellularresponse

Relay molecules in a signal transductionpathway

321

3) The 3 stages of cell signaling:

#1 reception#2 transduction#3 response

Signal Transduction

Which of the following best describes a signal transduction pathway?

A) binding of a signal molecule to a cell proteinB) catalysis mediated by an enzymeC) sequence of changes in a series of molecules

resulting in a responseD) binding of a ligand on one side of a membrane that

results in a change on the other sideE) the cell’s detection of a chemical or mechanical

stimulus

Signal Transduction

Which of the following best describes a signal transduction pathway?

A) binding of a signal molecule to a cell proteinB) catalysis mediated by an enzymeC) sequence of changes in a series of molecules

resulting in a responseD) binding of a ligand on one side of a membrane that

results in a change on the other sideE) the cell’s detection of a chemical or mechanical

stimulus

A steroid hormone binds to an intracellular receptor. When it does, the resulting complex is able to do which of the following? Why?

A. open channels in the membrane for other substances to enter

B. open channels in the nuclear envelope for cytoplasmic molecules to enter

C. mediate the transfer of phosphate groups to/from ATP

D. act as a transcription factor in the nucleusE. make water-soluble molecules able to diffuse across

membranes

A steroid hormone binds to an intracellular receptor. When it does, the resulting complex is able to do which of the following? Why?

A. open channels in the membrane for other substances to enter

B. open channels in the nuclear envelope for cytoplasmic molecules to enter

C. mediate the transfer of phosphate groups to/from ATP

D. act as a transcription factor in the nucleusE. make water-soluble molecules able to diffuse across

membranes

CascadeWithout consulting the figure in your text, describe what is

happening at each of the stages labeled 2 through 5.

Phosphorylation

In reactions mediated by protein kinases, what does phosphorylation of successive proteins do to drive the reaction?

A. make functional ATPB. change a protein from its inactive to its active formC. change a protein from its active to its inactive formD. alter the permeability of the cell’s membranesE. produce an increase in the cell’s store of inorganic

phosphates

Phosphorylation

In reactions mediated by protein kinases, what does phosphorylation of successive proteins do to drive the reaction?

A. make functional ATPB. change a protein from its inactive to its active formC. change a protein from its active to its inactive formD. alter the permeability of the cell’s membranesE. produce an increase in the cell’s store of inorganic

phosphates

Signal Molecules

What would happen to a cell whose receptors remain bound to the signal molecule(s)?

Which of the following is an example of signal amplification?

A) catalysis of many cAMP molecules by several simultaneously binding signal molecules

B) activation of 100 molecules by a single signal binding event

C) activation of a specific gene by a growth factor

D) activation of an enzyme moleculeE) utilization of a second messenger system

Which of the following is an example of signal amplification?

A) catalysis of many cAMP molecules by several simultaneously binding signal molecules

B) activation of 100 molecules by a single signal binding event

C) activation of a specific gene by a growth factor

D) activation of an enzyme moleculeE) utilization of a second messenger system

Cancer and Apoptosis

How could cancer result from a defect in apoptosis?

One of the important outcomes of apoptosis is protection of neighboring cells. Which of the following is responsible?

A. cell shrinkage and blebbingB. destruction of the cell’s DNAC. formation of numerous vesicles to be digestedD. action of tyrosine kinasesE. activation of specific proteins

One of the important outcomes of apoptosis is protection of neighboring cells. Which of the following is responsible?

A. cell shrinkage and blebbingB. destruction of the cell’s DNAC. formation of numerous vesicles to be

digestedD. action of tyrosine kinasesE. activation of specific proteins

What are the similarities among the following?

• G protein-coupled receptors

• receptor tyrosine kinases

• ion channel receptors