Download G protein

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Document related concepts
no text concepts found
Transcript
Cell Communication
PowerPoint® Lecture Presentations for
Biology
Eighth Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
 Cell-to-cell
communication is essential for
multicellular organisms
 Universal mechanisms of cellular
regulation
 Combined effects of multiple signals
determine cell response
 Example: dilation of blood vessels is
controlled by many molecules
• Nitric oxide
• Myosin
• Signaling molecule called MAP kinase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

Microbes are a window on the role of cell signaling in the evolution of life
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-2
 factor
Receptor
1
Exchange
of mating
factors

a
a factor
Yeast cell,
mating type a
2
Mating
3
New a/
cell
Yeast cell,
mating type 

a
a/
 Pathway
similarities suggest that ancestral
signaling molecules evolved in prokaryotes
and were modified later in eukaryotes
 Concentration of signaling molecules allows
bacteria to detect population density
• Cluster together
• Coordination of activities
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-3
1 Individual rodshaped cells
2 Aggregation in
process
0.5 mm
3 Spore-forming
structure
(fruiting body)
Fruiting bodies
 In
multicellular organisms, long distance
communication is by chemical messengers
 Local signaling
• intercellular connections (plasmodesmata and gap
junctions) connect the cytoplasm of adjacent cells
• communicate by direct contact, or cell-cell
recognition
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Local
Fig. 11-4
Plasma membranes
Gap junctions
between animal cells
(a) Cell junctions
(b) Cell-cell recognition
Plasmodesmata
between plant cells
 In
many other 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
Fig. 11-5
Local signaling
Long-distance signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Target cell
Secreting
cell
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling
Endocrine cell
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Target cell
is stimulated
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(b) Synaptic signaling
(c) Hormonal signaling
 Earl W. Sutherland
discovered how the
hormone epinephrine acts on cells
• 1971 Nobel Prize
 Cells
receiving signals went through three
processes:
• Reception (detection of signaling molecule)
• Transduction (converts signal to relay or form
that can bring about cell change)
• Response (enz. catalysis, cytoskeleton mvmt.
gene activation)
Animation: Overview of Cell Signaling
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-6-1
EXTRACELLULAR
FLUID
1 Reception
Receptor
Signaling
molecule
CYTOPLASM
Plasma membrane
Fig. 11-6-2
CYTOPLASM
EXTRACELLULAR
FLUID
Plasma membrane
1 Reception
2 Transduction
Receptor
Relay molecules in a signal transduction pathway
Signaling
molecule
Fig. 11-6-3
CYTOPLASM
EXTRACELLULAR
FLUID
Plasma membrane
1 Reception
2 Transduction
3 Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Signaling
molecule
 Binding
between signal molecules
(ligands) and receptors = highly specific
 Shape change in receptor -- initial
transduction of the signal
 Most signal receptors are plasma
membrane proteins
• Receptors for testosterone or estrogen are
cytoplasmic
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
 Water-soluble
signal molecules bind to
specific receptors in plasma membrane
• insulin
3
main types of membrane receptors:
• G protein-coupled receptors
• Receptor tyrosine kinases
• Ion channel receptors
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
 Widespread
& diverse functions
• Highly conserved throughout evolution
• vision & smell
 Plasma
membrane receptor that requires a
G protein
• acts as an on/off switch: when GDP is bound, the G
protein is inactive
• When GTP is bound, G protein is active
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7a
Signaling-molecule binding site
Segment that
interacts with
G proteins
G protein-coupled receptor
Fig. 11-7b
Plasma
membrane
G protein-coupled
receptor
Activated
receptor
Signaling molecule
Inactive
enzyme
GDP
CYTOPLASM
GDP
Enzyme
G protein
(inactive)
GTP
2
1
Activated
enzyme
GTP
GDP
Pi
Cellular response
3
4
Hormones & neurotransmitters
Bacterial toxins (cholera, pertussis, botulism) interfere w/ G proteins
 Plasma
membrane receptors that attach
phosphates to tyrosines
 Cell growth & cell reproduction
• Example: vascular endothelial growth factor
(VEGF) stimulates endothelial cells to undergo
cell division and migration to form new blood
vessels
 Ligand
binding triggers multiple signal
transduction pathways at once
• Key difference from G protein coupled receptors
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7c
Ligand-binding site
Signaling
molecule (ligand)
Signaling
molecule
 Helix
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
CYTOPLASM
Dimer
1
2
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
P Tyr
P Tyr
Tyr
Tyr
P
6 ATP
Activated tyrosine
kinase regions
6 ADP
Tyr
Tyr
P Tyr
Tyr
P
Tyr
P Tyr
P Tyr
Tyr
P
P
P
P
Tyr P
Tyr
Fully activated receptor
tyrosine kinase
Inactive
relay proteins
3
4
Cellular
response 1
Cellular
response 2
 Acts
as a gate when the receptor changes
shape upon binding ligand
- allows specific ions (Na+, K+, Cl- or
Ca2+) through the channel in the receptor
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7d
Na+/K+ ATPase
Ligand gated
ion channels
-neurotransmitters
in CNS
-acetylcholine at the
neuromuscular
junction
1 Signaling
molecule
(ligand)
Gate
closed
Ions
Ligand-gated
ion channel receptor
2
Plasma
membrane
Gate open
Cellular
response
3
Gate closed
 Found
in the cytosol or nucleus of target
cells
 Small
or hydrophobic chemical
messengers can readily cross the
membrane to activate receptors
• Examples: steroid and thyroid hormones
 Activated
hormone-receptor complex can
act as a transcription factor, turning on
specific genes
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-8-3
Hormone
(testosterone)
Intracellular
receptors
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-4
Hormone
(testosterone)
Intracellular
receptors
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
Fig. 11-8-5
Hormone
(testosterone)
Intracellular
receptors
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
 Transduction
involves many steps
 Signal amplification: a few molecules can
produce a large cellular response
 Provide many opportunities for
coordination and regulation of the cellular
response
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
 Molecules
that relay signals are mostly
proteins
 Like falling dominoes, receptors activate
another protein, which activates another,
and so on, until the protein producing the
cellular response is activated
 At each step, the signal is transduced into a
different form, usually a shape change in a
protein
 Carried out via phosphorylation chain
reaction
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
 Signals
transmitted by a cascade of
protein phosphorylations (adds negative
charge to protein & thus changes its
conformation)
 Protein kinases - enzymes that transfer
phosphates from ATP to protein, in a
process called phosphorylation
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
 Protein
phosphatases - enzymes that
remove the phosphates from proteins, a
process called dephosphorylation
 This phosphorylation and
dephosphorylation system acts as a
molecular switch, turning activities on and
off
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-9
Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
Pi
P
Active
protein
kinase
2
PP
Inactive
protein kinase
3
Pi
ATP
ADP
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response
 Amplify
cell’s response
 Different points at which response can be
regulated
 Specificity of response
• Different cells express different collections of
proteins
 e.g. liver cells and neurons
 Non-protein, water
soluble molecules or
ions
 Readily spread through cytoplasm
 Pathways
• G protein coupled receptors
• Receptor tyrosine kinases

Two most common
Cyclic AMP (cAMP)
 calcium

 Many
signaling molecules trigger
formation of cAMP
 Components
of cAMP pathways
• G proteins & G protein-coupled receptors
• protein kinases
 Activates
protein kinase A, which initiates
phosphorylation cascade
 Further
regulation of cell metabolism
• G-protein systems that inhibit adenylyl cyclase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-11
First messenger
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
cAMP
Second
messenger
Protein
kinase A
Cellular responses
 Calcium
ions (Ca2+) - second messenger in
many pathways
 Cells can easily regulate its concentration


Signal triggers an increase in cytosolic calcium
Other components involved:
inositol triphosphate (IP3)
 diacylglycerol (DAG)

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
as additional second messengers
Fig. 11-12
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2+ pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
ATP
Key
High [Ca2+]
Low [Ca2+]
Ca2+
pump
Fig. 11-13-3
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
PIP2
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Various
proteins
activated
Ca2+
Ca2+
(second
messenger)
Cellular
responses
1.
Describe the nature of a ligand-receptor
interaction and how such interactions initiate
a signal-transduction system
2.
Compare and contrast G protein-coupled
receptors, tyrosine kinase receptors,
hormone receptors, and ligand-gated ion
channels
1. Provide examples for each
3.
4.
List two advantages of a multistep signaling
cascade in the transduction stage of cell
signaling
Explain how an original signal molecule can
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
5.
Define the term second messenger; and
describe the role of these molecules in
signaling pathways
1. List two examples
6.
Explain why different types of cells may
respond differently to the same signal
molecule (section 11.4)
1. Provide an example
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Related documents