Genetic analysis of integrin function in man: LAD-1 and other syndromes

N Hogg, PA Bates - Matrix Biology, 2000 - Elsevier
N Hogg, PA Bates
Matrix Biology, 2000Elsevier
The integrins are cell membrane receptors composed of α and β subunits which orchestrate
adhesive events in all tissues of the body (Hynes, RO, 1992. Integrins: versatility,
modulation, and signalling in cell adhesion. Cell 69, 11–25; and Hynes, RO, 1999. Cell
adhesion: old and new questions. Trends Cell Biol. 9, M33–37). At present 18 α subunits
and 8 β subunits have been identified which are loosely organised into families. There are
three inherited autosomal recessive diseases in man which involve germline mutations in …
The integrins are cell membrane receptors composed of α and β subunits which orchestrate adhesive events in all tissues of the body (Hynes, R.O., 1992. Integrins: versatility, modulation, and signalling in cell adhesion. Cell 69, 11–25; and Hynes, R.O., 1999. Cell adhesion: old and new questions. Trends Cell Biol. 9, M33–37). At present 18 α subunits and 8 β subunits have been identified which are loosely organised into families. There are three inherited autosomal recessive diseases in man which involve germline mutations in genes coding for integrins. Leukocyte adhesion deficiency-1 (LAD-1) is the result of mutations in the β2 subunit of the CD11/CD18 integrins, LFA-1, Mac-1, p150,95 and αdβ2. The bleeding disorder Glanzmann thrombasthenia is caused by mutations in either the α or β subunit of the platelet integrin, αIIbβ3. Thirdly, it is now recognised than one of the variants of the usually lethal skin blistering disorder, epidermolysis bullosa (JEB-PA), is caused by mutation in either the α or β subunit of the epithelial hemidesmosome integrin, α6β4. Many of the mutations cause defective αβ heterodimer formation. The majority of the β subunit mutations are in the conserved N-terminal region known as the βI domain. It is suggested that this region participates in αβ heterodimer formation.
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