cell comunication p={'t':3}; var...
TRANSCRIPT
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
PowerPoint Lectures for Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Chapter 11
Cell Communication
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Overview: The Cellular Internet
• Cell-to-cell communication
– Is absolutely essential for multicellular organisms
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Biologists
– Have discovered some universal mechanisms of cellular regulation
Figure 11.1
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 11.1: External signals are converted into responses within the cell
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Evolution of Cell Signaling
• Yeast cells
– Identify their mates by cell signaling factor
Receptor Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type.
1
Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion.
New a/ cell. The nucleus of the fused cell includes all the genes from the a and a cells.
2
3
factorYeast cell,mating type a
Yeast cell,mating type
a/
a
a
Figure 11.2
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Signal transduction pathways
– Convert signals on a cell’s surface into cellular responses
– Are similar in microbes and mammals, suggesting an early origin
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Local and Long-Distance Signaling
• Cells in a multicellular organism
– Communicate via chemical messengers
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Animal and plant cells
– Have cell junctions that directly connect the cytoplasm of adjacent cells
Plasma membranes
Plasmodesmatabetween plant cells
Gap junctionsbetween animal cells
Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.
• In local signaling, animal cells
– May communicate via direct contact
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In other cases, animal cells
– Communicate using local regulators
(a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid.
(b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.
Local regulator diffuses through extracellular fluid
Target cell
Secretoryvesicle
Electrical signalalong nerve celltriggers release ofneurotransmitter
Neurotransmitter diffuses across
synapse
Target cellis stimulated
Local signaling
Figure 11.4 A B
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In long-distance signaling
– Both plants and animals use hormones
Hormone travelsin bloodstreamto target cells
(c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells.
Long-distance signaling
Bloodvessel
Targetcell
Endocrine cell
Figure 11.4 C
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Three Stages of Cell Signaling: A Preview
• Earl W. Sutherland
– Discovered how the hormone epinephrine acts on cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Sutherland suggested that cells receiving signals went through three processes
– Reception
– Transduction
– Response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
EXTRACELLULARFLUID
Receptor
Signal molecule
Relay molecules in a signal transduction pathway
Plasma membraneCYTOPLASM
Activationof cellularresponse
Figure 11.5
• Overview of cell signaling
Reception1 Transduction2 Response3
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• The binding between signal molecule (ligand)
– And receptor is highly specific
• A conformational change in a receptor
– Is often the initial transduction of the signal
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Intracellular Receptors
• Intracellular receptors
– Are cytoplasmic or nuclear proteins
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Signal molecules that are small or hydrophobic
– And can readily cross the plasma membrane use these receptors
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
DNA
mRNA
NUCLEUS
CYTOPLASM
Plasmamembrane
Hormone-receptorcomplex
New protein
Figure 11.6
• Steroid hormones
– Bind to intracellular receptors1 The steroid hormone testosterone passes through the plasma membrane.
The bound proteinstimulates thetranscription ofthe gene into mRNA.
4
The mRNA istranslated into aspecific protein.
5
Testosterone bindsto a receptor proteinin the cytoplasm,activating it.
2
The hormone-receptor complexenters the nucleusand binds to specific genes.
3
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Receptors in the Plasma Membrane
• There are three main types of membrane receptors
– G-protein-linked
– Tyrosine kinases
– Ion channel
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• G-protein-linked receptors
G-protein-linkedReceptor
Plasma Membrane
EnzymeG-protein(inactive)CYTOPLASM
Cellular response
Activatedenzyme
ActivatedReceptor
Signal molecule Inctivateenzyme
Segment thatinteracts withG proteins
GDP
GDP
GTP
GTP
P i
Signal-binding site
Figure 11.7
GDP
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Receptor tyrosine kinasesSignalmolecule
Signal-binding sitea
CYTOPLASM
Tyrosines
Signal moleculeHelix in the
Membrane
Tyr
TyrTyr
TyrTyr
TyrTyr
TyrTyr
TyrTyr
Tyr
Tyr
TyrTyr
TyrTyr
Tyr Tyr
TyrTyr
TyrTyr
Tyr
Tyr
TyrTyr
TyrTyr
Tyr
DimerReceptor tyrosinekinase proteins(inactive monomers)
PPP
PP
P Tyr
TyrTyr
TyrTyr
TyrP
PP
PP
PCellularresponse 1
Inactiverelay proteins
Activatedrelay proteins
Cellularresponse 2
Activated tyrosine-kinase regions(unphosphorylateddimer)
Fully activated receptortyrosine-kinase(phosphorylateddimer)
6 ATP 6 ADP
Figure 11.7
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Ion channel receptors
Cellularresponse
Gate open
Gate close
Ligand-gatedion channel receptor
Plasma Membrane
Signalmolecule(ligand)
Figure 11.7
Gate closed Ions
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell
• Multistep pathways
– Can amplify a signal
– Provide more opportunities for coordination and regulation
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Signal Transduction Pathways
• At each step in a pathway
– The signal is transduced into a different form, commonly a conformational change in a protein
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Protein Phosphorylation and Dephosphorylation
• Many signal pathways
– Include phosphorylation cascades
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In this process
– A series of protein kinases add a phosphate to the next one in line, activating it
– Phosphatase enzymes then remove the phosphates
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Signal molecule
Activeproteinkinase
1
Activeproteinkinase
2
Activeproteinkinase
3
Inactiveprotein kinase
1
Inactiveprotein kinase
2
Inactiveprotein kinase
3
Inactiveprotein
Activeprotein
Cellularresponse
Receptor
P
P
P
ATPADP
ADP
ADP
ATP
ATP
PP
PP
PP
Activated relaymolecule
i
Phosphorylation cascade
P
P
i
i
P
• A phosphorylation cascade
Figure 11.8
A relay moleculeactivates protein kinase 1.
1
2 Active protein kinase 1transfers a phosphate from ATPto an inactive molecule ofprotein kinase 2, thus activatingthis second kinase.
Active protein kinase 2then catalyzes the phos-phorylation (and activation) ofprotein kinase 3.
3
Finally, active proteinkinase 3 phosphorylates aprotein (pink) that brings about the cell’s response tothe signal.
4 Enzymes called proteinphosphatases (PP)catalyze the removal ofthe phosphate groupsfrom the proteins, making them inactiveand available for reuse.
5
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Small Molecules and Ions as Second Messengers
• Second messengers
– Are small, nonprotein, water-soluble molecules or ions
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cyclic AMP
• Cyclic AMP (cAMP)
– Is made from ATP
Figure 11.9
O–O O
O
N
O
OO
O
P P P
PP P
O
O
O
O
O
OH
CH2
NH2 NH2 NH2
N
N
N
N
N
N
N
NN
N
NO
O
O
ATP
Ch2 CH2
O
OH OH
P
O O
H2O
HOAdenylyl cyclase Phoshodiesterase
Pyrophosphate
Cyclic AMP AMPOH OH
O
i
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Many G-proteins
– Trigger the formation of cAMP, which then acts as a second messenger in cellular pathways
ATP
GTP
cAMP
Proteinkinase A
Cellular responses
G-protein-linkedreceptor
AdenylylcyclaseG protein
First messenger(signal moleculesuch as epinephrine)
Figure 11.10
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Calcium ions and Inositol Triphosphate (IP3)• Calcium, when released into the cytosol of a
cell
– Acts as a second messenger in many different pathways
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Calcium is an important second messenger
– Because cells are able to regulate its concentration in the cytosol
EXTRACELLULARFLUID
Plasmamembrane
ATP
CYTOSOL
ATP Ca2+
pump
Ca2+
pump
Ca2+
pump
Endoplasmicreticulum (ER)
Nucleus
Mitochondrion
Key High [Ca2+] Low [Ca2+]Figure 11.11
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Other second messengers such as inositol triphosphate and diacylglycerol
– Can trigger an increase in calcium in the cytosol
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.12
321
IP3 quickly diffuses throughthe cytosol and binds to an IP3–gated calcium channel in the ERmembrane, causing it to open.
4 The calcium ionsactivate the nextprotein in one or moresignaling pathways.
6 Calcium ions flow out ofthe ER (down their con-centration gradient), raisingthe Ca2+ level in the cytosol.
5
DAG functions asa second messengerin other pathways.
Phospholipase C cleaves aplasma membrane phospholipidcalled PIP2 into DAG and IP3.
A signal molecule bindsto a receptor, leading toactivation of phospholipase C.
EXTRA-CELLULARFLUID
Signal molecule(first messenger)
G protein
G-protein-linkedreceptor
Variousproteinsactivated
Endoplasmicreticulum (ER)
Phospholipase CPIP2
IP3
(second messenger)
DAG
Cellularresponse
GTP
Ca2+
(second messenger)
Ca2+
IP3-gatedcalcium channel
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 11.4: Response: Cell signaling leads to regulation of cytoplasmic activities or transcription
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cytoplasmic and Nuclear Responses
• In the cytoplasm
– Signaling pathways regulate a variety of cellular activities
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Cytoplasmic response to a signal
Figure 11.13Glucose-1-phosphate
(108 molecules)
Glycogen
Active glycogen phosphorylase (106)Inactive glycogen phosphorylase
Active phosphorylase kinase (105)Inactive phosphorylase kinase
Inactive protein kinase AActive protein kinase A (104)
ATPCyclic AMP (104)
Active adenylyl cyclase (102)
Inactive adenylyl cyclase
Inactive G protein
Active G protein (102 molecules)
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Response
Reception
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Other pathways
– Regulate genes by activating transcription factors that turn genes on or off
Reception
Transduction
Response
mRNANUCLEUS
Gene
P
Activetranscriptionfactor
Inactivetranscriptionfactor
DNA
Phosphorylationcascade
CYTOPLASM
ReceptorGrowth factor
Figure 11.14
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Fine-Tuning of the Response
• Signal pathways with multiple steps
– Can amplify the signal and contribute to the specificity of the response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Signal Amplification
• Each protein in a signaling pathway
– Amplifies the signal by activating multiple copies of the next component in the pathway
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Specificity of Cell Signaling
• The different combinations of proteins in a cell
– Give the cell great specificity in both the signals it detects and the responses it carries out
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Pathway branching and “cross-talk”
– Further help the cell coordinate incoming signals
Response 1
Response 4 Response 5
Response
2
Response
3
Signalmolecule
Cell A. Pathway leads to a single response
Cell B. Pathway branches, leading to two responses
Cell C. Cross-talk occurs between two pathways
Cell D. Different receptorleads to a different response
Activationor inhibition
Receptor
Relaymolecules
Figure 11.15
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
• Scaffolding proteins
– Can increase the signal transduction efficiency
Signalmolecule
Receptor
Scaffoldingprotein
Threedifferentproteinkinases
Plasmamembrane
Figure 11.16