A Cell Signal Relay
Posted February 1, 1998
When the adrenal gland releases adrenaline (epinephrine) into the blood stream, the heart muscle begins to beat faster and stronger. But adrenaline never enters the
heart muscle cells, so how does adrenaline signal the insides of the muscle cells to change how they function? A cellular version of the "telephone game" passes this information
from one molecule to the next.
Extracellular messengers, such as adrenaline, begin this "telephone game" by binding to specific proteins on the outer surface of target cells. These proteins serve
as very specific receptors. The "telephone game," a process called signal transduction, relays the signal to the inside of the cell. Many extracellular messengers relay their signals
through a class of proteins called G proteins. These G proteins direct the signals from the receptor proteins to the inside of the cell.
G proteins are so named because they bind to guanine nucleotides. G proteins are made up of three subunits — alpha, beta, and gamma. At rest, when the cell's
surface receptor is unoccupied, the three subunits are bound together and the alpha subunit is bound to a guanine diphosphate (GDP). When the external messenger (usually a hormone or
neurotransmitter, such as adrenaline) binds to the receptor, it stimulates a change in the shape of the receptor. This shape change causes the G protein to undergo a change as well.
The alpha subunit parts from the beta and gamma subunits and replaces the GDP with a quanine triphosphate (GTP). The alpha-GTP complex then moves along the plasma membrane's inner surface
and links to an internal effector, often an enzyme that switches on a series of reactions inside the cell. The alpha subunit itself is an enzyme a GTPase. The alpha subunit breaks down
the GTP to GDP and phosphate. This shuts off the signal and the alpha-GDP rejoins the beta and gamma subunits.
The discovery of G proteins has helped scientists better understand certain diseases, such as the intestinal disease cholera. Cholera bacteria secrete a toxin that
prevents the alpha subunit from converting GTP to GDP, locking mucus-secreting cells of the intestine in an "on" position. This results in a loss of large amounts of fluid, a symptom
of this disease.
Scientists are currently trying to unravel the transduction pathways of various hormones and neurotransmitters to help understand the "wiring" diagrams of the plasma
membrane. This will help scientists predict how cells will operate in response to combinations of signals. In the future, therapies for various disorders may be treated by specific drugs
that affect these signal transduction pathways.
References
Walton, W. R. "G Proteins: Prized for Their Role in Cell Signaling." BrainWork, Vol. 4:6, pp. 4-5
Linder, M.E. and A.G. Gilman. "G Proteins," Scientific American, Vol. 271:7, July 1992, pp. 56-65.
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