Cell Communication3d1: Cell communication processes share common features that reflect a

shared evolutionary history3d2: Cells communicate with each other through direct contract with

other cells or from a distance via chemical signaling3d3: Signal transduction pathways link signal reception with cellular

response3d4: Changes in signal transduction pathways can alter cellular response

DSJ – Pair Share

What is communication? What purpose does it serve? What are the different ways humans commuicate? Do other organisms (bacteria, plants, animals) communicate? Predict two ways cells might communicate with one another.

Overview

• Cell in a multicellular organism must communicate to coordinate activities lack of communication results in chaos

• Traffic signals image what traffic would be like without them• In studying how cells signal and interpret signals they

receive, biologists have discovered some universal mechanisms of communication; same small set of cell-signaling mechanisms show up again and again in many lines of biological research (bacteria, animals, plants, yeast)

Example of primitive cells communicating• Communications

between mating yeast:• Use chemical signals to

identify opposite mating types

• Cells of mating type a secrete a signal molecule called a factor, which can bind to receptors on nearby ∂ type cells

Receptor factor

a factor

a

a

Exchangeof matingfactors

Yeast cell,mating type a

Yeast cell,mating type

Mating

New a/cell

a/

1

2

3

Second Example of primitive cell communication

• Communication among bacteria:• Use chemicals to share information about

nutrient availability• When food is scarce, starving cells secrete

a molecule that reaches neighboring cells and stimulates them to aggregate forming a fruiting body that produces thick-walled spores capable of surviving until the environment improves

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

• Quorum sensing: bacteria’s ability to sense the local population size based on the concentration of signaling molecules

• Can lead to coordination of activities

• Biofilms: collections of bacteria that often form recognizable structures that contain regions of specialized functions.

Individual rod-shaped cells

Spore-formingstructure(fruiting body)

Aggregation inprocess

Fruiting bodies

0.5 mm

1

3

2

Three many ways cells communicate

• Direct contact (post-it note – direct – messages is hand transferred)

• Immune cells using antigen presenting cells• Plasmodesmata/Gap junctions

• Short Distance (email – sent to a specific individual)• Local Regulators such as neurotransmitters

• Long distances (Facebook – broadcasted to multiple cells)• Endocrine cells release hormones (chemicals) through blood to

communicate with target cells (cell meant to receive the message)

Direct Contact• Cell junctions: allow molecules to

pass between adjacent (touching) cells without crossing the plasma membrane

• Gap junctions: term used to refer to the junctions in animal cells

• Plasmodesmata: term used to refer to the junction in plant cells

• Cell-to-cell recognition: cells in animal cells may communicate by interaction between molecules protruding from their surfaces

Plasma membranes

Gap junctionsbetween animal cells

(a) Cell junctions

Plasmodesmatabetween plant cells

(b) Cell-cell recognition

Short Distance (Local Signaling)• Paracrine signaling:

• Secreting cell acts on multiple nearby cells by excreting local regulators

• Synaptic signaling: • cell releases

neurotransmitters molecules into a synapse, stimulating ONE target cell

• Local regulators: message molecules that travel short distances

Local signaling

Target cell

Secretoryvesicle

Secretingcell

Local regulatordiffuses throughextracellular fluid

(a) Paracrine signaling (b) Synaptic signaling

Target cellis stimulated

Neurotransmitter diffuses across synapse

Electrical signalalong nerve celltriggers release ofneurotransmitter

Long Distance Signaling

• Electrical signals along a nerve cell

• Hormones: chemicals released in the blood stream to target cells; secreted by endocrine glands/organs (pancreas, hypothalmus…)

Long-distance signaling

Endocrine cell Bloodvessel

Hormone travelsin bloodstreamto target cells

Targetcell

(c) Hormonal signaling

Signal Transduction Pathways

• A series of steps by which signal on a cell’s surface is converted into a specific cellular response

• Three processes: 1. Reception2. Transduction3. Response

EXTRACELLULARFLUID

Plasma membrane

CYTOPLASM

Receptor

Signalingmolecule

Relay molecules in a signal transduction pathway

Activationof cellularresponse

Transduction Response2 3Reception1

Signal Transduction Pathway: Reception• Reception: target cell detects the signaling

molecule; detection takes place when the signaling molecules binds to the receptor protein located at the cell’s surface or inside the cell

• Ligand: general name used to refer to the substance that binds to a receptor

• A shape change in the receptor is often the initial transductions of the signal

Reception1

EXTRACELLULARFLUID

Signalingmolecule

Plasma membrane

1

Receptor

Three main types of membrane receptors• G protein-coupled receptors: receptor that workswith

the help of a G protein• Receptor tyrosine kinases: attach phosphates to

tyrosines; can trigger multiple signal transduciton pathways at once

• Ion channel receptors: acts as a gate when receptor changes shape; gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

G protein-coupled receptor1. When GDP is bound to the G

protein, the G protein is inactive

2. When signaling molecule binds to receptor, receptor is activated and changes shape, shape change cause receptor to bind with G protein, causing GTP to displace GDP

3. Activated G protien travels from the receptor and binds with an enzyme, altering the enzymes shape and turning it on; the enzyme leads to a cellular response

4. G protein also acts as a GTPase enzyme (breaks down GTP to GDP. G protein becomes inactive again and is available to be reused

G protein-coupledreceptor

Plasmamembrane

EnzymeG protein(inactive)

GDP

CYTOPLASM

Activatedenzyme

GTP

Cellular response

GDP

P i

Activatedreceptor

GDP GTP

Signaling moleculeInactiveenzyme

1 2

3 4

Receptor Tyrosine KinasesSignalingmolecule (ligand)

Ligand-binding site

Helix

TyrosinesTyr

Tyr

Tyr

Tyr

Tyr

Tyr

Receptor tyrosinekinase proteins

CYTOPLASM

Signalingmolecule

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Dimer

Activated relayproteins

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

PPP

PPP

Cellularresponse 1

Cellularresponse 2

Inactiverelay proteins

Activated tyrosinekinase regions

Fully activated receptortyrosine kinase

6 6 ADPATP

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

PPP

PPP

1 2

3 4

1. Before the signaling molecules binds, the receptors exist as individuals polypeptides

2. Binding causes two receptor polypeptides to associate closely with each other, form a dimer (dimerization)

3. Dimerization activates the tyrosine kinase region of each polypeptide; each tyrosine kinase adds a phosphate from an ATP

4. Receptor protein is fully activated, recognized by relay proteins; each protein binds to a phosphorylated tyrosine, changes structure; each activated protein triggers a transduction pathway, leading to cellular response

Ion channel receptors1. Ligand-gated ion channel receptor in which

the gate remains closed until a ligand binds to the receptor

2. When the ligand binds to the receptor and the gate opens, specific ions can flow through the channel and rapidly change the concentration of that particular ion inside the cell. This change may directly affect the activity of the cell in some way.

3. When the ligand dissociates form this receptor, the gate closes and ions no longer enter the cell

Signalingmolecule(ligand)

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed3

2

1

Intracellular Receptors

• Some receptor proteins are intracellular, found in the cytoplasm or nucleus of target cells

• Small or hydrophobic chemical messengers can cross the membrane and activate receptors; examples = hormones

• Can act as a transcription factor (proteins that are needed to turn on genes)

Hormone(testosterone)

EXTRACELLULARFLUID

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

mRNA

NUCLEUS New protein

CYTOPLASM

Signal Transduction Pathway: Transduction• Signal transductions usually involves multiple steps; allows for amplification

of the signal, and opportunities for coordination and regulation• Like falling 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

• A receptor protein recognizes a signal molecule, causing the receptor protein to change shape which initiates transduction of the signal which ultimately leads to a response from the cell (movement of the cell, expression of a gene (transcription of DNA into mRNA).

• Can be thought of as a cascade

Protein Phosphorylation and Dephosphorylation• Many signal transduction pathways

occur as a result of a cascade of protein phosphorylation.

• Protein kinases: enzyme that transfers phosphates from ATP to protein

• This process is called phosphorylation

• Protein phosphatases: enzyme that removes the phosphates from proteins

• This process is called dephosphorylation

• This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off

Signaling molecule

ReceptorActivated relaymolecule

Inactiveprotein kinase

1 Activeproteinkinase

1Inactive

protein kinase2

ATPADP Active

proteinkinase

2

P

PPP

Inactiveprotein kinase

3

ATPADP Active

proteinkinase

3

P

PPP

i

ATPADP P

ActiveproteinPP

P i

Inactiveprotein

Cellularresponse

Phosphorylation cascadei

It’s not all about proteins

• Most of the molecules involved in Signal Transduction are proteins; however, there are small molecules that act as relay messengers and are often essential to the cascade, these molecules are called second messengers

• Two common second messengers are cyclic AMP (cAMP) and calcium ions

Cyclic AMP• cyclic adenosine monophosphate; cyclic

AMP; cAMP• An enzyme embedded in the plasma

membrane (adenylyl cyclase – you do not need to memorize the name of the enzyme) converts ATP to cAMP in response to an extracellular signal (such as epinephrine binding to a protein receptor)

• When epinephrine outside the cell binds to a specific receptor protein, the protein activates adenylyl cyclase, which in turn can catalyze the synthesis of many molecules of cAMP because enzyme is reusable cAMP can be boosted 20-fold in seconds

• cAMP usually activates protein kinase A, which phosphorylates various other proteins leading to a cellular response

First messenger

G proteinAdenylylcyclase

GTP

ATPcAMP

Secondmessenger

Proteinkinase A

G protein-coupledreceptor

Cellular responses

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

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

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 11-13-3

G protein

EXTRA-CELLULARFLUID

Signaling molecule(first messenger)

G protein-coupledreceptor Phospholipase C PIP2

DAG

IP3(second messenger)

IP3-gatedcalcium channel

Endoplasmicreticulum (ER) Ca2+

CYTOSOL

Variousproteinsactivated

Cellularresponses

Ca2+

(secondmessenger)

GTP

Nuclear and Cytoplasmic 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 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

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 11-14Growth factor

Receptor

Phosphorylationcascade

Reception

Transduction

Activetranscriptionfactor

ResponseP

Inactivetranscriptionfactor

CYTOPLASM

DNA

NUCLEUS mRNA

Gene

Fine-Tuning of the Response

• Multistep pathways have two important benefits:• Amplifying the signal (and thus the response)• Contributing to the specificity of the response

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Termination of the Signal

• Inactivation mechanisms are an essential aspect of cell signaling

• When signal molecules leave the receptor, the receptor reverts to its inactive state

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings