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