- Ligand-gated ion-channel receptors: These are responsible for the selective movement
of ions such as Naþ,Kþand Clacross membranes. Binding of the agonist triggers the
gating(opening) of a channel and the movement of ions across the membrane. This
ion movement is a short-term, fast response that results in the propagation of a
membrane potential wave. It may be excitatory and result in the depolarisation of the
cell (e.g. the nicotinic acetylcholine and ionotropic glutamate receptors), or inhibitory
(e.g. theg-aminobutyric acid A (GABAA) receptor). All receptors in this class consist of
four or five homo- or heteromeric subunits. Responses produced by this class of
receptors occur in fractions of a second. - G-protein-coupled receptors (GPCRs): Receptors in this class are linked to a
G-protein that is trimeric (i.e. it has three subunits). Receptor activation by
agonist binding triggers its interaction with a G-protein located within the cell
membrane and protruding into the cytoplasm resulting in the exchange of GTP
for GDP (hence the name G-protein) on one subunit that dissociates from the
trimer causing the activation of an effector molecule such as adenylyl cyclase
(also known as adenylate cyclase) that is part of an intricate network of intracellular
transduction pathways. Responses produced by GPCRs occur in the timescale
of minutes. - Protein kinase receptors: These receptors all undergo agonist-stimulated
autophosphorylation in their intracellular domain. This activates a kinase activity
within this domain. The majority of activated receptor kinases catalyse the transfer
of theg-phosphate of ATP to the hydroxyl group of a tyrosine in the target effector
protein, hence the termreceptor tyrosine kinases(RTKs). This phosphorylation
process controls the activity of many vital cell processes. Members of a minor
subgroup of protein kinase receptors transfer the phosphate group of ATP to a serine
or threonine group rather than tyrosine, hence the termreceptor serine
(orthreonine)kinases. Responses produced by protein kinase receptors occur over a
timescale of minutes to hours. Closely related to the protein kinase receptors is
a group of receptors that lack intrinsic protein kinase activity but which recruit a
non-receptor tyrosine kinase after agonist binding. The recruited kinase
phosphorylates tyrosine residues in the receptors’ intracellular domains then act
as recognition sites for other effector proteins which, when activated, translocate
to the cell nucleus where, in association with other regulatory proteins, they modify
gene expression. Responses to these receptors occur within a timescale of minutes
to hours.
Further details of the mechanism by which each of these three classes of receptor
induce the transduction process are discussed in Section 17.5. There is evidence that
many receptors exist in multipleisoformsthat have subtly different physiological
roles and that many receptors form homo- and/or heterodimers or oligomers that are
sensitive to allosteric regulation and which function as partners to initiate interactions
between the downstream signalling molecules triggered by each receptor. Thiscross-
talkbetween receptors allows cells to integrate signalling information originating
from various external sources and to respond to it with maximum regulatory
efficiency.662 Cell membrane receptors and cell signalling