Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1052 Chapter 19: Cell Junctions and the Extracellular Matrix
gap of
2–4 nm
(A)
two connexons in
register forming
open channel between
adjacent cells
interacting
plasma membranes
homomeric
channel
1.5 nm in
diameter
connexon
composed of
six subunits
(C)
heteromeric homotypic heterotypic
1.4 nm
Figure 19–25 Gap junctions. (A) A drawing
of the interacting plasma membranes
of two adjacent cells connected by gap
junctions. Each lipid bilayer is shown as
a pair of red sheets. Protein assemblies
called connexons (green), each of which
is formed by six connexin subunits,
penetrate the apposed lipid bilayers. Two
connexons join across the intercellular
gap to form a continuous aqueous
channel connecting the two cells. (B) The
organization of connexins into connexons,
and connexons into intercellular channels.
The connexons can be homomeric or
heteromeric, and the intercellular channels
can be homotypic or heterotypic. (C) The
high-resolution structure of a homomeric
gap-junction channel, determined by x-ray
crystallography of human connexin 26. In
this view, we are looking down on the pore,
formed from six connexin subunits. The
structure illustrates the general features of
the channel and suggests a pore size of
about 1.4 nm, as predicted from studies
of gap-junction permeability with molecules
of various sizes (see Figure 19–24).
(PDB code: 2ZW3.)
(B) connexins connexons
intercellular channels
Gap junctions in different tissues can have different properties because they
are formed from different combinations of connexins, creating channels that differ
in permeability and regulation.
MBoC6 m19.34/19.25
Most cell types express more than one type of
connexin, and two different connexin proteins can assemble into a heteromeric
connexon, with its own distinct properties. Moreover, adjacent cells expressing
different connexins can form intercellular channels in which the two aligned halfchannels
are different (see Figure 19–25B).
Like conventional ion channels (discussed in Chapter 11), individual gapjunction
channels do not remain open all the time; instead, they flip between open
and closed states. These changes are triggered by a variety of stimuli, including the
voltage difference between the two connected cells, the membrane potential of
each cell, and various chemical properties of the cytoplasm, including the pH and
concentration of free Ca 2+ . Some subtypes of gap junctions can also be regulated
by extracellular signals such as neurotransmitters. We are only just beginning to
understand the physiological functions and structural basis of these various gating
mechanisms.
Each gap-junctional plaque is a dynamic structure that can readily assemble,
disassemble, or be remodeled, and it can contain a cluster of a few to many
thousands of connexons (see Figure 19–23B). Studies with fluorescently labeled
connexins in living cells show that new connexons are continually added around
the periphery of an existing junctional plaque, while old connexons are removed
from the middle of it and destroyed (Figure 19–26). This turnover is rapid: the
connexin molecules have a half-life of only a few hours.
The mechanism of removal of old connexons from the middle of the plaque
is not known, but the route of delivery of new connexons to its periphery seems
clear: they are inserted into the plasma membrane by exocytosis, like other integral
membrane proteins, and then diffuse in the plane of the membrane until
they bump into the periphery of a connexon plaque and become trapped. This
has a corollary: the plasma membrane away from the gap junction should contain
connexons—hemichannels—that have not yet paired with their counterparts on
another cell. It is thought that these unpaired hemichannels are normally held
in a closed conformation, preventing the cell from losing its small molecules by