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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2217-2223.
Prepublished online as a Blood First Edition Paper on July 20, 2004; DOI 10.1182/blood-2004-04-1512.
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PLENARY PAPERS
CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin
Vanja Karamatic Crew,
Nicholas Burton,
Alexander Kagan,
Carole A. Green,
Cyril Levene,
Frances Flinter,
R. Leo Brady,
Geoff Daniels, and
David J. Anstee
From the Bristol Institute for Transfusion Sciences, National Blood Service, Bristol; the Department of Biochemistry, University of Bristol, Bristol, United Kingdom; the Department of Nephrology and Hypertension, Kaplan Medical Center (affiliated to Hebrew University-Hadassah Medical School), Rehovot, Israel; the National Blood Group Reference Laboratory, Magen David Adom, Blood Services Center, Ramat Gan, Israel; and the Evelina Children's Hospital, Guy's and St Thomas' NHS Trust, London, United Kingdom.
Tetraspanins are thought to facilitate the formation of multiprotein complexes at cell surfaces, but evidence illuminating the biologic importance of this role is sparse. Tetraspanin CD151 forms very stable laminin-binding complexes with integrins  3 1 and 61 in kidney and 31 and 64 in skin. It is encoded by a gene at the same position on chromosome 11p15.5 as the MER2 blood group gene. We show that CD151 expresses the MER2 blood group antigen and is located on erythrocytes. We examined CD151 in 3 MER2-negative patients (2 are sibs) of Indian Jewish origin with end-stage kidney disease. In addition to hereditary nephritis the sibs have sensorineural deafness, pretibial epidermolysis bullosa, and -thalassemia minor. The 3 patients are homozygous for a single nucleotide insertion (G383) in exon 5 of CD151, causing a frameshift and premature stop signal at codon 140. The resultant truncated protein would lack its integrin-binding domain. We conclude that CD151 is essential for the proper assembly of the glomerular and tubular basement membrane in kidney, has functional significance in the skin, is probably a component of the inner ear, and could play a role in erythropoiesis.
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