This animation depicts the surface view of a target cell and its interaction
with a peptide hormone as a model to demonstrate g-protein coupled signal
transduction in cells. Peptide hormones generally consist of
short chains of amino acids. Because peptide hormones are often quite short,
they lack a rigid three-dimensional conformation and are flexible.
Peptide hormones are usually water-soluble and too large to pass
through the lipid plasma membrane of their target cells.
Therefore peptide hormones interact with a cell surface receptor that has an
exposed extracellular hormonal binding site.
The peptide hormone fits into the receptor like a key fits into a lock, and
the hormonal message is conveyed to the receptor.
The activated receptor then undergoes a conformational change that transfers the
hormonal message into the cell.
Once inside the cell, the message is converted or transduced into unique chemicals referred to as second
messengers. The intracellular second messengers
control the cellular biochemistry to determine how the cell should respond to the hormone.
In this example the hormone stimulates the target cell to
open a membrane cation channel.
When the channel opens, cations enter the cell and cause a localized
depolarization that spreads over an area of the cell surface.
In this model, the localized depolarization of the cell membrane
represents the target cell response to the hormonal message.
Finally we fade into a view of the internal organization of the target cell
that shows the peptide hormone receptor and its chemicals for converting the
hormone message into the intracellular second messengers.
This scene will show the details of how
a target cell converts an external hormonal message into internal
second messengers that produce a cellular response.
The hormone receptor is a protein that has seven hydrophobic transmembrane-
spanning regions that project through the cell's plasma membrane.
The receptor is associated with a g-protein that is comprised of alpha,
beta and gamma subunits. The peptide hormone assumes its active configuration,
fits on to the receptor binding site and conveys its message. The message results
in a conformational change in the receptor that is transferred
mechanically to the g-protein mechanical activation of the g-protein
results in the alpha subunit replacing guanosine diphosphate with guanosine
triphosphate.
The activated alpha subunit separates from the beta and gamma subunits and migrates within
the plasma membrane to an inactive phospholipase C enzyme. Energy captured
from the hydrolysis of the terminal phosphate of guanosine triphosphate is
transferred through the alpha subunit to activate the phospholipase c.
The process of activating the phospholipase c converts the guanosine
triphosphate back to guanosine diphosphate, and the alpha subunit
rejoins the beta and gamma subunits to reform the inactive g-protein.
Activated phospholipase c degrades phospholipids that make up the plasma
membrane to produce two second messengers inositol one, fou,r five, tris-
phosphate and diacylglycerol.
1,4.5 Tris-phosphate is released from the membrane and binds to a receptor on the
endoplasmic reticulum. This intracellular signal results in the release of calcium
stored within the endoplasmic reticulum. The released calcium plus the
diacylglycerol from the membrane activate an inactive protein kinase
enzyme in the plasma membrane.
The previous scene demonstrated how second messengers transfer the primary
message from the hormone to activate an enzyme that will produce a physiological
response in the target cell. Activated protein kinase from the
previous scene facilitates the transfer of a high energy phosphate group from
adenosine triphosphate to an inactive cation channel protein.
Phosphorylation of the cation channel protein activates the channel protein
and causes opening of the cation channel.
Opening the cation channel allows extracellular cations such as sodium to
enter the cell. The diffusion of sodium into the cell results in a localized
depolarization of the cell membrane in the region of the channel.
The depolarization spreads across an area of the cell surface. Since this is
only a hypothetical model to explain g-protein signaling, the depolarization
is presumed to produce an important physiological response within the target
cell, or to signal other cells.
G-protein-coupled receptors are involved in numerous physiological actions
including: sensory responses to light and chemicals, as well as responding to
peptide hormones and other signaling chemicals such as neurotransmitters that
convey extracellular information. Because of their widespread use by cells for
signal transduction, g-protein coupled receptors are important targets in the
development of new pharmaceuticals for medical treatments.