Download Cell-cell communication Cell-cell communication is distance

8/20/13 Cell-cell communication
With over 75 trillion cells in the human body, we
need to understand how cells communicate with
one another.
The two primary ways that cells communicate are
either by electrical signals or chemical signals.
We will look at both in this section of the course.
Before we dive into this in too much detail, we
want to look at general trends in communication.
Cell-cell communication is distancedependent
You might communicate with someone
differently depending on how far they are from
you (next to you versus across the ocean, for
instance).
To some extent, cells are the same way.
Cell-cell communication is distancedependent
1. Gap Junctions
Cells that are right next to one another can communicate via protein
channels that directly link them together.
These proteins are called connexin proteins, and the channels that
are produced are called connexons.
These connexons can open or close (and do so under a variety of
cues); multiple things can pass through them (only way for electrical
signals to pass directly from cell-cell).
Also when they are open, they these tissues like one cell with
multiple nuclei (a syncytium).
What’s a cell that occurs without gap junctions that’s a syncytium?
1 8/20/13 Cell-cell communication is distancedependent
2. Contact-dependent signals
Requires that cells are in direct contact with one
another.
Common during growth and development, as well
as in the immune system (think about antigen
presentation, etc).
Cell-adhesion molecules (CAMs) often play a role
in contact-dependent signaling
Cell-cell communication is distancedependent
3. Autocrine & Paracrine signaling
A chemical is released into the local environment,
affecting only the nearby, surrounding, cells.
The biggest difference between autocrine and paracrine
signaling is the cell that responds to the signal:
If the cell that released the signal responds to it, this is
autocrine (auto = self); the cell is essentially activating
itself.
If a nearby cell responds to the signal, this is
paracrine.
2 8/20/13 Cell-cell communication is distancedependent
Everything we’ve talked about so far deals with cells that are close to one
another. Also, we’ve only talked about chemical signals.
What about cells that are long distances from each other?
Long-distance communication can be either electrical or chemical.
The endocrine system uses hormones to send messages over long distances
The nervous system uses both chemical and electrical signals to send
messages.
Neurocrines are the chemicals released by nervous system cells, and can be
classified as neurotransmitters, neurohormones, or neuromodulators.
Response to chemical signals
There are two questions to be addressed here:
1.  What causes some cells to respond to a signal,
and some to “ignore” it?
2.  If a cell does respond to a signal, how does it
respond?
The proteins found on the surface of the cell differ from cell-cell (what do you think causes
the difference?)
Some of the proteins found on the cell membrane or within the cell bind to signaling
molecules.
A cell can only respond to a signal if it has the proper receptor protein.
3 8/20/13 Response to chemical signals
There are two questions to be addressed here:
1.  What causes some cells to respond to a signal,
and some to “ignore” it?
The cell must have the proper receptor protein, either on its
membrane, or in the cytosol/nucleus
2.  If a cell does respond to a signal, how does it
respond?
If a cell does respond to a signal, how
does it respond?
The answer depends on whether the signaling
molecule is lipophilic or lipophobic.
Lipophilic molecules can diffuse through the
cell membrane; lipophobic molecules cannot.
Lipophobic molecules
tend to act on existing
thus they have
 proteins,
fast response time (ms to
min)
Lipophilic molecules bind receptors
either (a) in the cytosol, or (b) in
the nucleus. This messengerreceptor complex acts as a
transcription factor, and results in
initiation of transcription. This
either causes genes to be turned on
or off. Effects are slower to see (can
be hours).
 4 8/20/13 vs.
These are less common, but still
very important to our physiology
Response times of minutes to
hours
Results in transcriptions of new
proteins.
Binds receptors in cytosol or
nucleus
5 8/20/13 Signal transduction
Both receptor-enzymes and G-protein coupled
receptors use second messengers
learn to recognize names like cAMP, IP3, and DAG
as second messengers
Protein kinases are also important in
phosphorylating or dephosphorylating proteins
where do you think that phosphate might come
from?
But, other signaling molecules, like calcium, are
extremely important in physiology (we’ll see calcium
all the time this semester).
Turning the signal off
In order to maintain homeostasis, these signals
cannot be turned on forever; they must be turned
off at some point.
Homeostasis is regulated largely by reflex
pathways, which have two loops:
response loops
feedback loops
6 8/20/13 S-mulus e
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Output Signal Target Response Negative feedback example: home heating system
Negative feedback example: home heating system 7 8/20/13 Negative feedback example: home heating system Negative feedback example: home heating system Negative feedback example: home heating system 8 8/20/13 Negative feedback example: home heating system Negative feedback example: home heating system Negative feedback loops
Negative feedback loops are homeostatic
They stabilize the variable within the normal
range of function
They restore the normal state
9 8/20/13 Physiological setpoints can be changed either by acclimation
(done artificially in a lab) or by acclimatization (done
naturally).
Postive feedback loops:
Are NOT homeostatic
The response must be stopped by
some outside factor (in this example,
the delivery of the baby)
Other examples include the milk
letdown reflex during breastfeeding
10 8/20/13 11 8/20/13 Here, the effect is not addi-ve, but rather mul-plica-ve. One hormone seems to poten-ate the others. This is the concept of hormonal synergism. Hormones also commonly work antagonis-cally to one another, where one hormone negates (or balances) the effects of another. Insulin and glucagon are two really good examples of antagonis-c hormones. 12