Upload
rocio-selby
View
228
Download
0
Tags:
Embed Size (px)
Citation preview
Cell Communication
Chapter 11Local regulators – in the vicinitya.Paracrine signaling – nearbyCells are acted on by signalingCell (ie. Growth factor)b. Synaptic signaling-neurotrans-mitters cross the synapse (gap)Between nerve cell and target
Long Distance Signaling
• Hormones–Endocrine signaling–Plant growth regulators
Figure 11.4 Plasma membranes
Gap junctionsbetween animal cells
Plasmodesmatabetween plant cells
(a) Cell junctions
(b) Cell-cell recognition
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
The Three Stages of Cell Signaling: A Preview
–Reception–Transduction–Response
© 2011 Pearson Education, Inc.
Receptors in the Plasma Membrane
• There are three main types of membrane receptors
–G protein-coupled receptors–Receptor tyrosine kinases–Ion channel receptors
© 2011 Pearson Education, Inc.
ligand-gated ion channel receptor • acts as a gate when the receptor
changes shape• signal molecule binds as a ligand to
the receptor• the gate allows specific ions, such as
Na+ or Ca2+, through a channel in the receptor
© 2011 Pearson Education, Inc.
Figure 11.7d
Signalingmolecule (ligand)
21 3
Gate closed Ions
Ligand-gatedion channel receptor
Plasmamembrane
Gate open
Cellularresponse
Gate closed
G-protein-coupled receptor (GPCRs• works with the help of a G protein• The G protein acts as an on/off switch
• If GDP is bound to the G protein, the G protein is inactive
© 2011 Pearson Education, Inc.
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
• Receptor tyrosine kinases (RTKs)• membrane receptors that attach
phosphates to tyrosines• can trigger multiple signal
transduction pathways at once• Abnormal functioning of RTKs is
associated with many types of cancers
© 2011 Pearson Education, Inc.
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
Intracellular Receptors
• found in the cytosol or nucleus of target cells• Small or hydrophobic chemical messengers
can activate receptors• Examples of hydrophobic messengers are the
steroid and thyroid hormones of animals• An activated hormone-receptor complex can
act as a transcription factor, turning on specific genes
© 2011 Pearson Education, Inc.
• A ligand-gated ion channel receptor acts as a gate when the receptor changes shape
• When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor
© 2011 Pearson Education, Inc.
Figure 11.7d
Signalingmolecule (ligand)
21 3
Gate closed Ions
Ligand-gatedion channel receptor
Plasmamembrane
Gate open
Cellularresponse
Gate closed
Intracellular Receptors
• found in the cytosol or nucleus of target cells• Small or hydrophobic chemical messengers
can readily cross the membrane and activate receptors
• Examples of hydrophobic messengers are the steroid and thyroid hormones of animals
• An activated hormone-receptor complex can act as a transcription factor, turning on specific genes
© 2011 Pearson Education, Inc.
Figure 11.9-5Hormone(testosterone)
Receptorprotein
Plasmamembrane
EXTRACELLULARFLUID
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
Signal Transduction Pathways
• mostly proteins• Produces a domino affect• At each step, the signal is transduced
into a different form, usually a shape change in a protein
© 2011 Pearson Education, Inc.
Protein Phosphorylation and Dephosphorylation
• Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation
• Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation
© 2011 Pearson Education, Inc.
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 11.10
Activated relaymolecule
Phosphorylation cascade
Inactiveprotein kinase
1 Activeprotein kinase
1
Activeprotein kinase
2
Activeprotein kinase
3
Inactiveprotein kinase
2
Inactiveprotein kinase
3
Inactiveprotein
Activeprotein
ATPADP
ATPADP
ATPADP
PP
PP
PP
P
P
P i
P i
P i
P
Figure 11.10a
Cyclic AMP
• Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal
• Cholera – regulating G protein for salt and water secretion. No GTP to GDP stimulates more cAMP
• cGMP – relaxes smooth muscles – effects of viagra
© 2011 Pearson Education, Inc.
Figure 11.11
Adenylyl cyclase Phosphodiesterase
Pyrophosphate
AMP
H2O
ATP
P iP
cAMP
Calcium Ions and Inositol Triphosphate (IP3)
• Calcium is an important second messenger because cells can regulate its concentration
• Lower in cytosol than extracellular (10,000x)
• Active transport of Ca++ out or from cytosol to ER and mitochondria (IP3 and DAG)
© 2011 Pearson Education, Inc.
Figure 11.13
Mitochondrion
EXTRACELLULARFLUID
Plasmamembrane
Ca2
pump
Nucleus
CYTOSOL
Ca2
pump
Ca2
pump
Endoplasmicreticulum(ER)
ATP
ATP
Low [Ca2 ]High [Ca2 ]Key
• A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol
• Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers
© 2011 Pearson Education, Inc.
Animation: Signal Transduction Pathways
Nuclear and Cytoplasmic Responses
• regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus
• The final activated molecule in the signaling pathway may function as a transcription factor
© 2011 Pearson Education, Inc.
Figure 11.15Growth factor
ReceptorReception
Transduction
CYTOPLASM
Response
Inactivetranscriptionfactor
Activetranscriptionfactor
DNA
NUCLEUS mRNA
Gene
Phosphorylationcascade
P
Fine-Tuning of the Response
• There are four aspects of fine-tuning to consider– Amplifying the signal (and thus the response)– Specificity of the response (liver/heart)– Overall efficiency of response, enhanced by
scaffolding proteins (brain)– Termination of the signal
© 2011 Pearson Education, Inc.
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.
Figure 11.19
Signalingmolecule
Receptor
Plasmamembrane
Scaffoldingprotein
Threedifferentproteinkinases
Concept 11.5: Apoptosis integrates multiple cell-signaling pathways
• Apoptosis is programmed or controlled cell suicide
• Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells
• Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells
© 2011 Pearson Education, Inc.
Figure 11.20
2 m
Apoptotic Pathways and the Signals That Trigger Them
• Caspases - the main proteases that carry out apoptosis
• triggered by–An extracellular death-signaling ligand –DNA damage in the nucleus–Protein misfolding in the endoplasmic
reticulum
© 2011 Pearson Education, Inc.