Essential Cell Biology 5th edition

548 CHAPTER 16 Cell Signaling
a different type of G protein, called G i because it inhibits adenylyl cyclase.
In this case, however, modification by the toxin disables the G protein
by locking it into its inactive GDP-bound state. Inhibiting G i , like activating
G s , results in the prolonged and inappropriate activation of adenylyl
cyclase, which, in this case, stimulates coughing. Both the diarrheaproducing
effects of cholera toxin and the cough-provoking effects of
pertussis toxin help the disease-causing bacteria move from host to host.
Some G Proteins Directly Regulate Ion Channels
There are about 20 different types of mammalian G proteins, each
activated by a particular set of cell-surface receptors and dedicated to
activating a particular set of target proteins. These target proteins are
either enzymes or ion channels in the plasma membrane. Thus, the binding
of an extracellular signal molecule to a GPCR leads to changes in the
activities of a specific subset of the possible target proteins in the plasma
membrane, producing a response that is appropriate for that signal and
that type of cell.
We look first at an example of direct G-protein regulation of ion channels.
The heartbeat in animals is controlled by two sets of nerves: one
speeds the heart up, the other slows it down. The nerves that signal
a slowdown in heartbeat do so by releasing acetylcholine (see Figure
16−5A), which binds to a GPCR on the surface of the heart pacemaker
cells. This GPCR activates the G protein, G i . In this case, the βγ complex
binds to the intracellular face of a K + channel in the plasma membrane
of the pacemaker cell, forcing the ion channel into an open conformation
(Figure 16–17A and B). This channel opening slows the heart rate by
increasing the plasma membrane’s permeability to K + , which makes it
more difficult to electrically activate, as explained in Chapter 12. The
original signal is terminated—and the K + channel recloses—when the
α subunit inactivates itself by hydrolyzing its bound GTP, returning the
G protein to its inactive state (Figure 16–17C).
acetylcholine
plasma membrane
closed K + channel
(A)
GTP
activated α subunit
K + CHANNEL
OPENING
activated
βγ complex
open K + channel
K +
EXTRACELLULAR SPACE
(B)
Figure 16–17 A G i protein directly
couples receptor activation to the
opening of K + channels in the plasma
membrane of heart pacemaker cells.
(A) Binding of the neurotransmitter
acetylcholine to its GPCR on the heart cells
results in the activation of the G protein, G i .
(B) The activated βγ complex directly opens
a K + channel in the plasma membrane,
increasing its permeability to K + and thereby
making the membrane harder to activate
and slowing the heart rate. (C) Inactivation
of the α subunit by hydrolysis of its bound
GTP returns the G protein to its inactive
state, allowing the K + channel to close.
(C)
CYTOSOL
P
inactive
G protein
GTP
GDP
G-PROTEIN
INACTIVATION;
K + CHANNEL
CLOSING
closed K + channel