PHYSIOLOGY 364
SIGNAL TRANSDUCTION
,PURPOSE OF SIGNAL TRANSDUCTION
The main goal of signal transduction is to define the mechanisms that cells, tissues and
organisms use to respond to physiological and environmental stimuli. Cells respond to
different environmental signals, stressors and toxins; all of which have profound
implications for the diversity of human
health and diseases. These include:
• Development
• Cystic fibrosis
• Diabetes
• Asthma
• Heart diseases
• Autoimmune diseases
• Cancer
Coordination of various activities of
cells throughout the body depends on
the ability of cells to communicate with
one another in order to accomplish life-
sustaining functions and other desired
responses.
COMMUNICATION BETWEEN CELLS
Intercellular communication can take place either directly
or indirectly. Direct intercellular communication involves
physical contact between the interacting cells:
Firstly, cells directly communicate through gap junctions
and possibly tunneling nanotubes. The most intimate means
of intercellular communication is through gap junctions, the
minute tunnels that bridge the cytoplasm of neighboring cells in
some tissue types. These tunnels are called connexons and
consist of 6 protein subunits arranged in a tube-like structure. 2
connexons from adjacent membranes extend outward and
join end-to-end to form a tunnel, and the small diameter allows
small, H20 soluble particles to pass through. Through gap
junctions, ions and small molecules are directly exchanged
between closely associated interacting cells without ever
entering the ECF.
Gap junctions are especially abundant in cardiac and smooth
muscle tissues. The movement of ions through these junctions
transmits electrical signals throughout the muscle fibre, which
results in contraction. The presence of gap junctions allows
synchronized contraction of the whole muscle, such as the
pumping of a chamber of the heart. Gap junctions are also
,found in non-muscle tissues allowing unrestricted passage of nutrient molecules between
cells.
Glucose, amino acids and other nutrients pass through junctions to the developing egg
cell in the ovary, which aids in storage of essential nutrients.
Tunneling nanotubes (TNTs), which are long, thin, hollow filaments, have recently been
discovered as a possible new route for direct intercellular exchange of materials. These
form transiently between cells that grow in the lab and various other cell types and have
been confirmed to exist in living tissues. Studies suggest that these intercellular bridges
serve as a route for selective, relatively long transfer from one cell to another of large
cargo, including proteins or organelles such as mitochondria. While cells that are
connected by gap junctions are in close proximity to one another (2 to 4nm apart), TNTs
may extend over a distance up to 150um between cells. Additionally, the opening in a
gap junction is 1.5nm in diameter compared to the much larger 50 to 200nm diameter
opening of a TNT. Because of these major differences between gap junctions and TNTs,
TNTs are able to transfer larger cargo over considerably longer distances than gap
junctions can. Motor proteins in TNTs are believed to help move substances through these
long tunnels. Additionally, viruses including HIV can hijack TNTs to move directly between
cells without entering the ECF.
Secondly, cells can directly communicate through the
transient direct linkup of surface markers. Some cells, such
as those of the immune system, have specialized markers
on the surface membrane that allow them to directly link
with certain other cells that have compatible markers for
transient interactions. This is how cell-destroying immune
cells specifically recognize and selectively destroy only
undesirable cells, such as cancer cells, while leaving the
body’s healthy cells alone.
The most common form of intercellular communication is indirect communication through
extracellular chemical messengers, or signal molecules, of which there are 4 types:
, 1. Paracrine/autocrine
2. Neurotransmitters
3. Hormones
4. Neurohormones
In each case, a specific chemical messenger, the signal molecule, is synthesized by
specialized controlling cells to serve a designated purpose. On being released into the
ECF following appropriate stimulation, these extracellular chemical messengers act on
other particular cells, known as target cells, in a prescribed manner. To exert this effect, an
extracellular chemical messenger must bind to specific receptors on the target cell
membrane.
A given cell may have thousands to a few million receptors, of which hundreds, if not
hundreds of thousands, may be for the same chemical messenger. Different cell types
have distinct combinations of receptors, allowing them to react individually to various
regulatory extracellular chemical messengers. Nearly 5% of all genes in humans code for
the synthesis of these membrane receptors, which indicates the importance thereof.
The four types of extracellular chemical messengers differ in their source and the distance
to and their transportation to their site of action.
Paracrine and Autocrine
Paracrine signals are local chemical
messengers whose effect is exerted only on
neighboring cells in the immediate environment
of their site of secretion. An autocrine is even
more localized; after being secreted, it acts
only on the cell that secreted it.
Because paracrine chemicals are distributed by simple diffusion within the interstitial fluid,
their action is restricted to short distances. They do not gain entry to the blood in any
significant quantity because they are rapidly inactivated by locally existing enzymes. An
example of a paracrine is histamine, which is released from a specific type of connective
