The Cell - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 20

Ions
Plasma membrane
Receptor
Signal
Figure 1.8 Signal transduction via ion channel-linked receptor.
responses to a wide variety of signals and produce diverse response like the sensa-
tions of taste, smell, perception of light, and so on. Although there are several sub-
classes of this large family of receptors, they have a certain structural similarity. All
these receptors are made up of a protein that traverses the membrane seven times,
that is, has seven transmembrane passes.
In response to an extracellular signal, the receptor undergoes a conformational
change to activate a membrane-attached trimeric G protein located on the cytosolic
side of the receptor. The G proteins are also a large family, and each responds to a
specific set of signals. The structure of G proteins is composed of three subunits—
, , and . The -subunit has a guanosine diphosphate (GDP) bound to it in the
unstimulated state. The G protein activation causes the  unit to exchange GDP for
GTP; simultaneously, it detaches from the - complex. These two separate parts of
the G protein move along the plasma membrane; they can bind with target proteins to
relay the signal, and their intensity of binding decides the strength and length of the
signal relay. The  unit slowly hydrolyzes back its GTP to GDP and returns back to
relink with the other two units, stopping the signal transduction. The target proteins
for G proteins may be enzymes, ion-gated channels, and so forth.
The interactions through an ion channel bring immediate change in the response
of the cell. For example, the slowing down of heart muscles in response to the
release of acetylcholine is mediated through a G protein-coupled receptor. The ace-
tylcholine activates a G protein, causing it to break apart into parts, and the - com-
plex opens the K  channel, changing its electrical properties ( Fig. 1. A).
The G protein-coupled receptors also interact with other enzymes; these often
include adenylyl cyclase and phospholipase C. The adenylyl cyclase pathway uses
cyclic adenosinemonophosphate (cyclic AMP) as the intracellular-signaling molecule,
and the phospholipase C pathway involves inositol trisphosphate and diacylglycerol.
These small molecules are termed the second messengers. The G protein's detached
 unit affects the adenylyl cyclase activity and increases the intracellular levels of