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

1076 Chapter 19: Cell Junctions and the Extracellular Matrix
epithelial
cell
keratin filaments
hemidesmosome
basal lamina
(A)
keratin
BP230
plectin
integrin
(α 6 β 4 )
collagen XVII
laminin
collagen
In epithelia, the most prominent cell–matrix attachment sites are the hemidesmosomes,
where a specific type of integrin anchors the cells to laminin in the
basal lamina. Here, uniquely, the intracellular attachment is to keratin intermediate
filaments, via the intracellular adaptor proteins plectin and BP230 (Figure
19–56).
(B)
Figure 19–56 Hemidesmosomes.
(A) Hemidesmosomes spot-weld epithelial
cells to the basal lamina, linking laminin
outside the cell to keratin filaments
inside it. (B) Molecular components of a
hemidesmosome. A specialized integrin
(α 6 β 4 integrin) spans the membrane,
attaching to keratin filaments intracellularly
via adaptor proteins called plectin and
BP230, and to laminin extracellularly. The
adhesive complex also contains, in parallel
with the integrin, an unusual collagen
family member known as collagen type
XVII; this has a membrane-spanning
domain attached to its extracellular
collagenous portion. Defects in any of
these components can give rise to a
blistering disease of the skin. One such
disease, called bullous pemphigoid, is an
autoimmune disease in which the immune
system develops antibodies against
collagen XVII or BP230.
Integrin Defects Are Responsible for Many Genetic Diseases
Although there is some overlap in the activities of the different integrins—at least
five bind laminin, for example—it is the diversity of integrin functions that is more
MBoC6 m19.46/19.57
remarkable. Table 19–3 lists some varieties of integrins and the problems that
result when individual integrin α or β chains are defective.
The β 1 subunit forms dimers with at least 12 distinct α subunits and is found
on almost all vertebrate cells: α 5 β 1 is a fibronectin receptor and α 6 β 1 is a laminin
Table 19–3 Some Types of Integrins
Integrin Ligand* Distribution Phenotype when α subunit
is mutated
α 5 β 1 Fibronectin Ubiquitous Death of embryo; defects
in blood vessels, somites,
neural crest
α 6 β 1 Laminin Ubiquitous Severe skin blistering;
defects in other epithelia also
α 7 β 1 Laminin Muscle Muscular dystrophy;
defective myotendinous
junctions
Phenotype when β subunit is
mutated
Early death of embryo
(at implantation)
Early death of embryo
(at implantation)
Early death of embryo
(at implantation)
α L β 2 (LFA1)
Ig superfamily
counterreceptors
(ICAM1)
White blood cells
Impaired recruitment of
leucocytes
Leukocyte adhesion deficiency
(LAD); impaired inflammatory
responses; recurrent lifethreatening
infections
α IIb β 3 Fibrinogen Platelets Bleeding; no platelet
aggregation (Glanzmann’s
disease)
Bleeding; no platelet
aggregation (Glanzmann’s
disease); mild osteopetrosis
α 6 β 4 Laminin Hemidesmosomes in
epithelia
*Not all ligands are listed.
Severe skin blistering;
defects in other epithelia also
Severe skin blistering; defects in
other epithelia also