regulation - cells need to control cellular processes. environmental stimuli - cells need to be...
TRANSCRIPT
Chapter 11Cell Communication
Why do cells communicate?
Regulation - cells need to control cellular processes.
Environmental Stimuli - cells need to be able to respond to signals from their environment.
Evolution of Cell Signaling
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-2
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
Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
In many cases, animal cells communicate using local regulators, messenger molecules that travel only short distances
In long-distance signaling, plants and animals use chemicals called hormones
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Cell Communication
Stages of C.S.
1. Reception - receiving the signal.2. Transduction - passing on the
signal.3. Response - cellular changes
because of the signal.
Reception
Transduction
Response
Reception
The target cell’s detection of a signal coming from outside the cell.
May occur by: Direct Contact Through signal molecules
Direct Contact
When molecules can flow directly from cell to cell without crossing membranes.
Plants - plasmodesmata Animals - gap junctions
Direct Contact
May also occur by cell surface molecules that project from the surface and “touch” another cell.
Signal Molecules
The actual chemical signal that travels from cell to cell.
Often water soluble. Usually too large to travel through
membranes. Double reason why they can’t
cross cell membranes.
Signal Molecules
Behave as “ligands”: a smaller molecule that binds to a larger one.
Receptor Molecules
Usually made of protein. Change shape when bind to a signal
molecule. Transmits information from the
exterior to the interior of a cell.
Receptor Mechanisms
1. G-Protein linked2. Tyrosine-Kinase3. Ion channels4. Intracellular
G-protein linked
Plasma membrane receptor. Works with “G-protein”, an
intracellular protein with GDP or GTP.
G-protein
GDP and GTP acts as a switch. If GDP - inactive If GTP - active
G-protein
When active (GTP), the protein binds to another protein (enzyme) and alters its activation.
Active state is only temporary.
Fig. 11-7b
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
G-protein linked receptors
Very widespread and diverse in functions.
Ex - vision, smell, blood vessel development.
G-protein linked receptors
Many diseases work by affecting g-protein linked receptors.
Ex - whooping cough, botulism, cholera, some cancers
G-protein linked receptors
Up to 60% of all medicines exert their effects through G-protein linked receptors.
Tyrosine-Kinase Receptors
Extends through the cell membrane. Intracellular part functions as a
“kinase”, which transfers P from ATP to tyrosine on a substrate protein.
Mechanism
1. Ligand binding - causes two receptor molecules to aggregate.
2. Activation of Tyrosine-kinase parts in cytoplasm.
3. Phosphorylation of tyrosines by ATP.4. After phophorylation, receptor
protein fully activated and is recognized by specific relay proteins in cell
Fig. 11-7c
Signalingmolecule (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
P
P
P
P
P
P
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
P
P
P
P
P
P
1 2
3 4
Tyrosine-Kinase Receptors
Often activate several different pathways at once, helping regulate complicated functions such as cell division.
Ion-channel Receptors
Protein pores in the membrane that open or close in response to chemical signals.
Allow or block the flow of ions such as Na+ or Ca2+.
Ion-channel Receptors
Activated by a ligand on the extracellular side.
Causes a change in ion concentration inside the cell.
Ex - nervous system signals.
Intracellular Proteins
Become activated & cause the cellular response.
Intracellular Signals
Proteins located in the cytoplasm or nucleus that receive a signal that CAN pass through the cell membrane.
Ex - steroids (hormones), NO - nitric oxide
Intracellular Signals
Activated protein turns on genes in nucleus.
Fig. 11-8-1
Hormone(testosterone)
Receptorprotein
Plasmamembrane
EXTRACELLULARFLUID
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-2
Receptorprotein
Hormone(testosterone)
EXTRACELLULARFLUID
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-3
Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-4
Hormone(testosterone)
EXTRACELLULARFLUID
PlasmamembraneReceptor
protein
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
Fig. 11-8-5
Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS New protein
CYTOPLASM
Video cliphttp://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__intracellular_receptor_model.html
Signal-Transduction Pathways
Often has multiple steps using relay proteins such as Protein Kinases
Question #9: amplification of signal provide more opportunities for
coordination and regulation of the cellular response
Protein Phosphorylation
Protein kinases transfer phosphates from ATP to protein… phosphorylation (this activates the protein)
Protein phosphatases remove the phosphates from proteins… dephosphorylation
Acts as a molecular switch
Fig. 11-9
Signaling molecule
ReceptorActivated relaymolecule
Inactiveprotein kinase
1 Activeproteinkinase
1
Inactiveprotein kinase
2
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
Amplification
Protein Kinases often work in a cascade with each being able to activate several molecules.
Result - from one signal, many molecules can be activated.
Secondary Messengers
Small water soluble, non-protein molecules or ions that pass on a signal.
Spread rapidly by diffusion. Activates relay proteins. Examples - cAMP, Ca2+
cAMP
A form of AMP made directly from ATP by Adenylyl cyclase (enzyme)
Short lived - converted back to AMP (by Phosphodiesterase)
Activates a number of Protein Kinases which then phosphorylates various other proteins
First messengerFig. 11-11
G protein
Adenylylcyclase
GTP
ATP
cAMPSecondmessenger
Proteinkinase A
G protein-coupledreceptor
Cellular responses
http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__second_messenger__camp.html
Calcium Ions
More widely used than cAMP. Used as a secondary messenger in
both G-protein pathways and tyrosine-kinase receptor pathways.
Works because of differences in concentration between extracellular and intracellular environments. (10,000X)
Involved in muscle cell contraction and cell division
EXTRACELLULARFLUID
Fig. 11-12
ATP
Nucleus
Mitochondrion
Ca2+ pump
Plasmamembrane
CYTOSOL
Ca2+
pumpEndoplasmicreticulum (ER)
Ca2+
pumpATP
Key
High [Ca2+]
Low [Ca2+]
Inositol Trisphosphate (IP3)
Secondary messenger attached to phospholipids of cell membrane.
Sent to Ca channel on the ER.Allows flood of Ca2+ into the
cytoplasm from the ER, which activate the next protein in one or more signaling pathways
(video animation from Campbell)11_13SignalTransduction_A.swf
Start here Or Start here
Cellular Responses
#18 Cytoplasmic Regulation Transcription Regulation in the
nucleus (DNA --> RNA).
Cytoplasmic Regulation
Rearrangement of the cytoskeleton. Opening or closing of an ion channel. Alteration of cell metabolism.
Transcription Regulation (Nucleus)
Activating protein synthesis for new enzymes.
Transcription control factors are often activated by a Protein Kinase.
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
http://highered.mcgraw-hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/0072437316/120069/bio08.swf::Signal%20Amplification
Specificity of Cell Signaling
Different kinds of cells have different collections of proteins (allows cells to detect and respond to different signals)
Same signal can have different effects in cells with different proteins and pathways
Pathway branching and “cross-talk” further help the cell coordinate incoming signals
Scaffolding Proteins
-Large relay proteins to which other relay proteins are attached
-Can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway
Fig. 11-18
Signalingmolecule
Receptor
Scaffoldingprotein
Plasmamembrane
Threedifferentproteinkinases
Apoptosis
Programmed or controlled cell suicide
A cell is chopped and packaged into vesicles that are digested by scavenger cells
Prevents enzymes from leaking out of a dying cell and damaging neighboring cells
Fig. 11-19
2 µm
Fig. 11-20
Ced-9protein (active)inhibits Ced-4activity
Mitochondrion
Receptorfor death-signalingmolecule
Ced-4 Ced-3
Inactive proteins
(a) No death signal
Ced-9(inactive)
Cellformsblebs
Death-signalingmolecule
Otherproteases
ActiveCed-4
ActiveCed-3
NucleasesActivationcascade
(b) Death signal
Summary Don’t get bogged down in details
in this chapter. Use the KISS principle.
Know : 3 stages of cell signaling examples of a receptor and how it
works protein kinases and cascades
(amplification) example of a secondary messenger