How do cells
Communicate...
a - in
multi-cell organisms contact between cells is critical for inter-cell
communication*.
b
- cell membranes contain specific
protein RECEPTORS, which bind &/or transmit
extra-cellular SIGNAL MOLECULES converting signals into specific
cellular responses.
Some UNIVERSAL PRINCIPLES of cell
communication are now well understood:
- cells use many different
signal molecules and receptors, for many cell
functions.
- and a simple mechanism
of signal/reception has survived throughout
evolution.
- an analogy: auto industry...
cars basically have same parts (engines, fenders,
lights)
and the variety of different shapes and patterns may
be boundless.
A key mechanism of Cell
to Cell Signaling is SIGNAL TRANSDUCTION*...
Here an exogenous signal
molecule is
received by a cell receptor and,
converted (transduced)
into a response by
the receiving cell.
This pattern is
remarkably similar in all
cells; probably evolved very
early,
even before multicellularity (maybe even in
single cell prokaryotes),
and has been
highly conserved in today's progeny of
ancestral cells.
__________________________________________________________________________________________
Cell Signaling can be LOCAL
or DISTANT...
PARACRINE (local) SIGNALING:
local regulator chemical messengers are targeted
to specific receptors
often includes: growth
factor proteins that promote cell
division & growth
& neurotransmitters
that move across synapses to other neurons
ENDOCRINE
(distant) SIGNALING:
examples*
specialized cells release molecules (often hormones) into blood
vessels of
circulatory system, hormones move to distant
target cells... elicit response
__________________________________________________________________________________________
Cell to Cell SIGNALING
SYSTEMS... a few examples...
haploid
cell mating in yeast cells*
(picture
of asexual budding in yeast cells)
sex-1
["a"-cell : releases a-factor (peptide of 12
aa's) - binds to sex-2 receptors]
sex-2
["α"-cell : releases α-factor - binds to
sex-1 receptors]
the result is fusion of 2
cells (a mating) producing diploid cell.
__________________________________________________________________________________________
__________________________________________________________________________________________
COMMUNICATION
via CELL-TO-CELL CONTACT:
- is where signaling is due to direct contact
exchanges...
- probably how cell communication
may have begun?
gap
junctions & plasmodesma...
results in cytoplasmic continuity favoring
cellular interactions...
fig 11.4a*
cell surface
contacts...
receptor protein specificity (as above with yeast cells)...
cell to cell contact is likely how
multicellularity began?
fig
11.4b*
__________________________________________________________________________________________
Cell Signaling often works via MOLECULAR SWITCHES...
examples*
the
universal model of a Signal Transduction Process
has 3 stages...
RECEPTION,
TRANSDUCTION, and
RESPONSE
1st. RECEPTION... is not unlike recognition of enzyme for
its substrate [ES complex]
...
akin to the lock-&-key
hypothesis of enzyme-substrate recognition
(Km & Vmax*)
...
ligand (signal) molecules
(usually water soluble) are recognized
by
only one
receptor protein bound within a cell
membrane.
2nd. TRANSDUCTION...
a conformation change in a receptor leads to
... shape and activity changes in other
intra-cellular molecules
...
which may result in multiple, conformational changes
in other cellular proteins
a cascade*
of inactive
enzymes
---> active enzymes,
& so on, etc...
3rd. RESPONSE... usually
a cellular activity,
as enzyme activation or catalysis,
or
rearrangement of cytoskeleton
(movement), or specific gene activity.
a Generic
Example of a
Receptor Protein & Signal Transduction
System:
G-Proteins
& G-Protein Coupled Receptors... GPCR's
membrane receptor proteins that bind GTP/GDP &
switch between
active
& inactive
forms. Some 50 to 100 GTP binding G-protein are
estimated.
(R.
Lefkowitz & B. Kobilka - 2012 Nobel
Prize-GPCRs)
G-protein
receptor structure... has 7
transmembrane α-helicies
& has site for signal
molecule and G-protein
to bind
fig 11.8a*
a signal molecule
binds to a receptor -&-> conformational
change occur -->
G-protein structure* is
inactive when GDP is bound to alpha subunit.
an inactive G-(GDP)-protein
now binds GTP (replacing
GDP)...
and active G-(GTP)-protein stimulates other
inactive enzymes...
fig 11.8b*
adenylyl cyclase
structure*
if G-Protein has its
GTP hydrolyzed -->
it inactivates
G-protein...
(Cholera & Botulin toxins...
keep G-proteins active --> diarrhea).
an Example of Scale
via G-protein responses involving a 2nd
messenger molecule:
"Fight or Flight Response"...
(see fig
11.12*) is due to a
phosphorylation
cascade
magnification... 1 signal molecule gives
multiple-enhanced response -
fig
11.16*
Summary
animation of glycogen breakdown*review
another
examples:
another 2nd messenger =
IP3 & Ca ions*
While the basics of Signal
Transduction are simple in design
the specificity of cell signaling
is varied among cells and can lead to a...
a
Multiplicity of Signal Transduction Responce
Mechnaisms*
cAMP
signaling is extensive in cellular function*
Specific Case Examples:
1.
Aldosterone reception & kidney regulation
- Campbell 11e- figure
11.15*
2. Ligand gated ion channel
signaling
- Campbell 11e- figure 11.8*
3.
Cortisol and nuclear receptors
- Campbell 11e- figure 11.15*
4. Signal
Transduction of gene activation
- Signals & Gene Action*review
a Summary review of
Receptors in Cells*review
copyright c2024 Last
update - March 2024
Charles
Mallery,
Department of Biology, U.of
Miami, Coral Gables, FL 33124
bckac.
next lecture.
you are not
responsible for the material that follows below:
- Janus tyrosine kinase &
inflammation*
other examples of Receptor Proteins
& Signal Transduction Systems...
2. Tyrosine
Kinase receptors... receptor
proteins that have kinase activity...
i.e., they can add a -PO4
group to tyrosine residues of inactive proteins
making them active --->
cell
response
fig 11.8*
many growth factors (stimulate cell division &
growth) function via tyr-kinases
... binding of growth factor (signal ligand)
causes 2 single tyr-kinases to aggregate
... the
tyr-dimers, now each phosphorylate the others tyr
residues via ATP kinase activity
... the
activated-phosphorylated dimer binds relay proteins,
activating them,
which in turn (by cascade effect) can active up to
10 others, etc...
net result... 1
signal molecule can trigger many proteins and
multiple pathways.
more examples of Receptor Proteins
& Signal Transduction Systems...
3. Ion
channel Receptors... [ligand gated protein
channels]
a protein PORE
in a membrane opens in response to
binding a signal molecule
ex: a
neurotransmitter as acetylcholine
(Ach) opens channel and lets Na+ ions
flood into cell, changing that cell's electrical
charge (potential) see fig
11.9*
How
Potassium ion Channel works - 2003 Nobel
Prize in Chemistry H2O
4. Non-membrane bound
[cytoplasmic - intracellular]
Receptors...
signal molecules diffuse through membrane, where
binding to an
intracellular receptor protein
initiates a cellular response.
ex: steroid hormones (see fig 11.10*)
back to
outlines
key
concepts*
copyright
c2010 Last
update -
next
Charles Mallery,
Biology 150, Department of Biology,
University of Miami, Coral Gables, FL 33124
Home |About |News |Syllabus |Lecture-outlines |Links |FAQ |Sitemap |Contact
the material below is not
required reading.
Review of Some Important Points of SIGNAL
TRANSDUCTION PATHWAYS
most are like dominos... one activates another, then
another, then another...
producing a significant cascade multiplication
effect.
1. an Enzyme
Cascade* - a
model phosphorylation cascade effect...
enzyme activation is by protein phosphorylation by
protein kinase enzymes,
that transfer P from ATP to another enzyme protein,
thereby activating it.
2. 2nd
messenger signal
molecules...
cyclic-AMP
[cAMP
= see
fig 11.11*]
signal molecule (hormone epinepherine) leads to
activation
of membrane bound inactive enzyme Adenyl Cyclase
ATP
---
active adenyl cyclase--->
cyclic-AMP
( cAMP is inactivated by phosphodiesterase ).
G-protein
& cAMP activation of
protein-kinase-A
see fig
11.12*
PKA, itself a kinase, can
activate other proteins, etc...
(see
epinepherine & glycogen breakdown
- see fig
11.15*
some
more POINTS of cell communication via signal
transduction:
3. cholera
toxin
Vibrio cholerae grow in fecal infected waters,
infect small intestine,
produce
toxin, which binds to a G-protein, prevents
conversion of GTP --> GDP,
thus
G-protein remains active, causing cAMP to remain
active....
net
result: small intestine secretes water and salts =
perfuse diarrhea = fatal.
4. Ca ions
cells maintain
a low cytoplasmic [Ca] by active transport of Ca out
of cytoplasm
pumps keep a
low cytoplasmic [Ca], but high ER cisternae &
mitoplasm [Ca]
see fig
11.14*
Ca itself functions as a 2nd messenger,
like cAMP,
as [Ca] in cytoplasm goes
up, activates Ca+ pumps, & other responses
ensue...
as
muscle contractions, neurotransmitter release,
etc...
5.
plant phytochrome action via
G protein & Ca channels = greening*
plant pigment involved in responses to light -
seed germination, photoperiodism, flowering,
etc...
6. gene activation via cascading
signal
transduction.
see fig
11.17*
5. Other 2nd messengers
and Ca activation...
Diacylglycerol (DAG) and
Inositol Triphosphate (IP
3)
a. signal molecule binds to a G-protein or a
tyrosine-kinase receptor
b.
G-protein activates
phospholipase-C, an enzyme that
splits lipids
c.
phospholipase-C splits the phospholipid, PIP 2, into DAG &
IP 3
d.
IP 3, as a ligand, binds to Ca ion
channel of ER and increases cytosol [Ca]
e. increased
Ca binds to enzyme calmodulin, changes its
conformation, which
f.
activates additional kinases and/or
phosphatases. see figure *
Some specific examples of G-protein
cellular responses:
mouse embryos lacking one G-protein... show no blood
vessel development
some human embryos w/o G-proteins... decreased
senses (esp: vision & smell)
cholera and botulin toxins... function by
interfering w G-proteins.
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