Transcript cell signaling in class

Cell Communication
1.Cells need to communicate
2. Cells have several mechanisms
for communicating
We are going to learn about several
of these mechanisms!
Local Signaling (short distances)
• Cells in a multicellular organisms communicate by
chemical messengers
• In local signaling, animal cells may communicate
by direct contact
• Animal and plant cells have cell junctions
(remember; gap junctions and plasmodesmata)
that directly connect the cytoplasm of adjacent
cells
LE 11-3
Plasma membranes
Gap junctions
between animal cells
Cell junctions
Cell-cell recognition
Plasmodesmata
between plant cells
Local Signaling (short distances) – con’t
• In many other cases, animal cells communicate
using local regulators, messenger molecules that
travel only short distances
Local signaling
Target cell
Secreting
cell
Local regulator
diffuses through
extracellular fluid
Paracrine signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Target cell
is stimulated
Synaptic signaling
Long-Distance Signaling
Long-distance signaling
In long-distance
signaling, plants and
animals use chemicals
called hormones
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
Hormonal signaling
The Three Stages of Cell Signaling: A Preview
• Earl W. Sutherland discovered how the hormone
epinephrine acts on cells
• Sutherland suggested that cells receiving signals
went through three processes:
– Reception
– Transduction - conversion of signal to a form
that can bring about a response
– Response
Reception
• Signal molecule (ligand)
binds to receptor
– Highly specific
– Conformational change in receptor often initiates
transduction of the signal
• Receptors found in two places
– Intracellular receptors found inside the cell (in
cytoplasm or nucleus)
– Plasma membrane receptors bind to water-soluble
ligands
Intracellular Receptors
• Some receptor proteins are intracellular, 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
LE 11-6
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
The steroid
hormone testosterone
passes through the
plasma membrane.
Testosterone binds
to a receptor protein
in the cytoplasm,
activating it.
The hormonereceptor complex
enters the nucleus
and binds to specific
genes.
DNA
The bound protein
stimulates the
transcription of
the gene into mRNA.
mRNA
NUCLEUS
New protein
The mRNA is
translated into a
specific protein.
CYTOPLASM
Receptors in the Plasma Membrane
• Most water-soluble signal molecules bind to
specific sites on receptor proteins in the plasma
membrane
• There are three main types of membrane
receptors:
– G-protein-linked receptors
– Receptor tyrosine kinases
– Ion channel receptors
• A G-protein-linked receptor is a plasma membrane
receptor that 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
• http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter1
7/animation__membranebound_receptors_that_activate_g_proteins.html
• http://www.dnatube.com/video/4254/G-ProteinReceptor-Animation
LE 11-7ab
Plasma
membrane
G-protein-linked
receptor
Activated
receptor
Signal molecule
GDP
CYTOPLASM
Enzyme
G protein
(inactive)
GDP
GTP
Activated
enzyme
GTP
GDP
Pi
Cellular response
Inactive
enzyme
LE 11-7b
Signal
molecule
Signal-binding site
a Helix in the
membrane
Signal
molecule
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
CYTOPLASM
Dimer
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
6
ATP
Activated tyrosinekinase regions
(unphosphorylated
dimer)
6 ADP
P Tyr
P Tyr
P Tyr
Tyr
P
P
Tyr P
Tyr
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
P Tyr
P Tyr
P Tyr
P
Tyr P
Tyr P
Tyr
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
• Receptor tyrosine kinases are membrane
receptors that attach phosphates to tyrosines
• A receptor tyrosine kinase can trigger multiple
signal transduction pathways at once
• http://faculty.plattsburgh.edu/donald.slish/tyrosinek
inase/tk1.html
• http://www.dnatube.com/video/4097/TK-ReceptorAnimation
• http://www.dnatube.com/video/539/ReceptorTyrosine-Kinase-Activation-and-Signalling
• An 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
• http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter2/ani
mation__receptors_linked_to_a_channel_protein.html
LE 11-7c
Signal
molecule
(ligand)
Gate
closed
Ligand-gated
ion channel receptor
Ions
Plasma
membrane
Gate open
Cellular
response
Gate closed
Transduction: Cascades of molecular interactions relay signals
from receptors to target molecules in the cell
• Transduction usually involves multiple steps
• Multistep pathways can amplify a signal: A few
molecules can produce a large cellular response
• Multistep pathways provide more opportunities for
coordination and regulation
LE 11-5_2
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane
Reception
Transduction
Receptor
Relay molecules in a signal transduction
pathway
Signal
molecule
Signal Transduction Pathways
• The molecules that relay a signal from receptor to
response are mostly proteins
• 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 conformational change
Protein Phosphorylation and Dephosphorylation
• In many pathways, the signal is transmitted by a
cascade of protein phosphorylations (adding of a
phosphate)
• Phosphatase enzymes remove the phosphates
• This phosphorylation and dephosphorylation system
acts as a molecular switch, turning activities on and
off
• Some pathways involve small, nonprotein watersoluble molecules or ions called second
messengers (ex. Calcium ions & Cyclic AMP)
Small Molecules and Ions as Second Messengers
• Second messengers are small, nonprotein, watersoluble molecules or ions
• The extracellular signal molecule that binds to the
membrane is a pathway’s “first messenger”
• Second messengers can readily spread
throughout cells by diffusion
• Second messengers participate in pathways
initiated by G-protein-linked receptors and
receptor tyrosine kinases
Cyclic AMP
• Cyclic AMP (cAMP) is one of the most widely used
second messengers
• Adenylyl cyclase, an enzyme in the plasma
membrane, converts ATP to cAMP in response to
an extracellular signal
LE 11-9
Phosphodiesterase
Adenylyl cyclase
Pyrophosphate
P
ATP
H2O
Pi
Cyclic AMP
AMP
• Many signal molecules trigger formation of cAMP
• Other components of cAMP pathways are G
proteins, G-protein-linked receptors, and protein
kinases
• cAMP usually activates protein kinase A, which
phosphorylates various other proteins
• Further regulation of cell metabolism is provided
by G-protein systems that inhibit adenylyl cyclase
LE 11-10
First messenger
(signal molecule
such as epinephrine)
Adenylyl
cyclase
G protein
G-protein-linked
receptor
GTP
ATP
cAMP
Second
messenger
Protein
kinase A
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
LE 11-11
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2+
pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
ATP
Key
Ca2+
pump
High [Ca2+]
Low [Ca2+]
• 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 second messengers
LE 11-12_1
EXTRACELLULAR Signal molecule
FLUID
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
IP3-gated
calcium channel
Endoplasmic
Ca2+
reticulum (ER)
CYTOSOL
Phospholipase C
PIP2
IP3 (second
messenger)
LE 11-12_2
EXTRACELLULAR Signal molecule
FLUID
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
Phospholipase C
IP3 (second
messenger)
IP3-gated
calcium channel
Endoplasmic
Ca2+
reticulum (ER)
CYTOSOL
PIP2
Ca2+
(second
messenger)
LE 11-12_3
EXTRACELLULAR Signal molecule
FLUID
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
Phospholipase C
PIP2
IP3 (second
messenger)
IP3-gated
calcium channel
Endoplasmic
Ca2+
reticulum (ER)
CYTOSOL
Ca2+
(second
messenger)
Various
proteins
activated
Cellular
responses
Response: Cell signaling leads to regulation of
cytoplasmic activities or transcription
• The cell’s response to an extracellular signal is
sometimes called the “output response”
• 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 pathways regulate the activity of enzymes
LE 11-5_3
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane
Reception
Transduction
Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction
pathway
Signal
molecule
Response
• Cell signaling leads to regulation of transcription or
cytoplasmic activities
– Protein synthesis
– Turn genes on or off
– Transcription factors
– May affect activity of enzymes
– May cause cytoskeleton rearrangement
LE 11-13
Reception
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Inactive G protein
Active G protein (102 molecules)
Inactive adenylyl cyclase
Active adenylyl cyclase (102)
ATP
Cyclic AMP (104)
Inactive protein kinase A
Active protein kinase A (104)
Inactive phosphorylase kinase
Active phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Response
Glycogen
Glucose-1-phosphate
(108 molecules)
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