How do cells Communicate...
in multi-cell organisms
cell-to-cell contact is critical.
- cell membranes
contain specific protein-receptors, which
bind & transmit
extra-cellular signal molecules
converting signals into specific cellular responses.
Some UNIVERSAL PRINCIPLES of cell
communication are now well known
cells may use many different signal molecules,
but only a few mechanisms have survived throughout evolution.
analogy: auto industry...
cars basically have same parts (engines, fenders, lights)
but the variety of different patterns is boundless.
TRANSDUCTION* is most common
method of CELL
here an exogenous
molecule is received by a cell,
(transduced) into a response by the receiving cell.
pattern is remarkably
similar in all cells; probably evolved very early,
even before first multi-cellular cells (maybe in single cell prokaryote);
and has been highly conserved in today's ancestral cells.
an EXAMPLE of COMMUNICATION...
CELL to CELL SIGNALING SYSTEMS
in yeast cells*
sex-1 ["a"-cell : releases a-factor
(peptide of 12 aa's) -
binds to sex-2 receptors]
: releases a-factor -
binds to sex-1 receptors]
results = is
fusion of 2 cells (mating) producing
Signaling can be LOCAL
PARACRINE (local) SIGNALING
local regulator chemical messengers are targeted to specific receptors
growth factor proteins that promote cell division & growth
neurotransmitters that move across synapses to other neurons
ENDOCRINE (distant) SIGNALING
specialized cells release molecules (often
hormones) into blood vessels of
circulatory system, hormones move to distant target cells... elicit response
- here the signaling is direct:
gap junctions & plasmodesma...
results in cytoplasmic continuity favoring cellular interactions...
cell surface contacts...
receptor protein specificity
(as above with yeast cells)...
The 3 Stages of Cell Signaling
or the Properties of a
Signal Transduction Pathway...
RECEPTION, TRANSDUCTION, and
Reception... is not unlike recognition of enzyme
akin to the lock-&-key hypothesis of enzyme-substrate recognition
(Km & Vmax)
... ligand molecules (usually water soluble) are
receptor protein bound within a cell membrane
Transduction... leads to a conformation change in receptor
... shape change results in receptor interacting with other intra-cellular molecules
... may result in multiple,
conformational/structural changes in other cellular proteins
inactive enzymes --->
active enzymes, & so on, etc...
Response... usually a cellular activity, as enzyme catalysis, or
the rearrangement of cytoskeleton
(movement), or specific gene activity.
Example of a Receptor Protein & Signal Transduction System
G-Protein Receptors... receptor
proteins that bind
& convert between active &
G-protein receptor structure...
has 7 transmembrane
& has site site for receptor molecule and
G-protein to bind
a signal molecule binds
to a receptor --> conformation change -->
G-(GDP)-protein now binds GTP (replacing GDP)...
other inactive enzymes.
G-Protein has its
GTP hydrolyzed --> inactivates G-protein
cholera and botulin
toxins... bind to G-protein keeping it active -->
specific example of
G-protein cellular responses:
Fight of Flight Response... (see
1 signal molecule gives multiple-enhanced response.
Concept Activity - Chapter 11.4 -
Build a Signaling pathway
specificity of cell signaling is varied
end cell communication
and leads to a multiplicity of
Other example of signal
1. Gene activation by a growth factor
- Campbell 8e-
2. Steroid hormone reception & myosin protein synthesis
- Campbell 8e -
3. Ligand gated ion channel signaling
- Campbell 8e -
4. IP3-DAG and Ca signaling
- Campbell 8e -
these signaling mechanism model themselves after the basic
signal transduction mechanism. example.
you are not responsible for the material that follows
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
making them active
many growth factors (stimulate cell division & growth) function via
... binding of growth factor (signal
ligand) causes 2 single tyr-kinases to
... 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
more examples of Receptor Proteins & Signal Transduction Systems...
channel Receptors... [ligand gated protein channels]
PORE in a membrane
opens in response to binding a signal molecule
ex: a neurotransmitter as acetylcholine
(Ach) opens channel and lets
flood into cell, changing that cell's electrical charge (potential)
How Potassium ion Channel works
2003 Nobel Prize in Chemistry
Non-membrane bound [cytoplasmic
signal molecules diffuse through membrane, where
binding to an
intracellular receptor protein initiates a cellular response.
ex: steroid hormones (see fig
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Charles Mallery, Department of Biology, University of
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Last Update -
July 18, 2008
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.
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.
2nd messenger signal molecules...
signal molecule (hormone epinepherine) leads to activation
of membrane bound inactive enzyme
active adenyl cyclase---> cyclic-AMP
cAMP is inactivated by phosphodiesterase ).
cAMP activation of protein-kinase-A
PKA, itself a kinase, can activate other proteins,
(see epinepherine &
glycogen breakdown -
some more POINTS of cell communication via signal transduction:
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.
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]
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...
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.
5. Other 2nd messengers and Ca
and Inositol Triphosphate (IP
a. signal molecule binds to a G-protein or a tyrosine-kinase
b. G-protein activates phospholipase-C, an enzyme that
c. phospholipase-C splits the phospholipid, PIP
2, into DAG & 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.