Cell Junctions, Structure, Function, and Regulation
343
but appears to be independent of myosin
II. Importantly, the stimulation of focal ad-
hesion formation by external forces leads
to activation of integrin signaling with
physiological consequences. For example,
increases in blood flow result in en-
hanced hemodynamic shear stress placed
on integrin-mediated adhesions on the
basal surface of endothelial cells, result-
ing in the remodeling of adhesion sites and
the activation of integrin signaling. The in-
creased integrin signaling and subsequent
changes in gene expression are thought to
play an important role in the development
of atherosclerotic plaques. Thus, integrin-
mediated adhesions are important sites at
which cells sense and respond to changes
in their physical environment, a process
referred to as mechanotransduction.
1.5
Hemidesmosomes
The
basal
layer
of
strati±ed
epithelia
mediate specialized adhesions to their
underlying basement membrane. These
specialized adhesions are referred to as
hemidesmosomes.
α
6
β
4
integrins are the
only
integrins present
at
hemidesmo-
somes, and function as critical trans-
membrane links between their ligand
laminin 5 in the basement membrane and
the keratin ±lament cytoskeleton within
the cell. The cytoplasmic domain of the
β
4
subunit plays an important role in
this linkage (Fig. 8), by binding to the
cytoskeletal linker proteins plectin and
BP230,
which,
in
turn,
can
bind
di-
rectly to intermediate ±laments. BP180
Laminin 5
Basement
membrane
Plasma
membrane
BP180
(Basal
lamina)
BP230
a
6
Keratin filaments
Plectin
BP180
BP180
Plectin
BP230
Plectin
b
4
a
6
b
4
a
6
b
4
Fig. 8
Hemidesmosomes. Hemidesmosomes are sites of strong adhesion between cells and
their underlying basement membrane. The
α
6
β
4
integrin binds to its ligand laminin-5 in the
basement membrane. The transmembrane protein BP180 has a collagenous extracellular domain
that forms a trimer and associates with the basement membrane on the outside of the cell. The
cytoplasmic domain of BP180 binds to the
β
4
tail and plectin on the inside of the cell. Both
plectin and BP230 function in linking
α
6
β
4
to keratin Flaments within the cell.
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