The integrin chains beta 1 and alpha 6 associate with the chaperone calnexin prior to integrin assembly.
Integrins are alpha beta heterodimers that mediate cell-cell adhesion, as well as cell-substrate adhesion. The largest subclass is formed by 10 heterodimers (the very late antigens) that all share the beta 1-chain. We have found a 90-kDa protein that co-isolates with mouse integrin beta 1-chain. This 90-kDa protein was identified as the mouse homolog of calnexin, a membrane-bound chaperone and resident protein of the endoplasmic reticulum. First, the sequence of the 15 NH2-terminal amino acids of the 90-kDa protein is 80% and 87% identical to the corresponding sequences of canine and human calnexin, respectively. Second, the 90-kDa protein was recognized by a monoclonal antibody against calnexin/IP90. Association of calnexin with the integrin beta 1-chain was directly demonstrated by chemical cross-linking. As pulse-chase experiments revealed, the association of the beta 1-chain with calnexin occurred prior to the assembly with integrin alpha 6-chain. Additionally, the alpha 6-chain bound to calnexin before integrin assembly and dissociated again at the time of integrin-assembly. Our data suggest that calnexin is involved in the assembly of beta 1 integrins, as well as in the retention of a pool of immature integrin beta 1-chains in the ER.
Lenter
M
M
Hans-Spemann Laboratorium am Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Vestweber
D
D
D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D037281:Calnexin; D002460:Cell Line; D003545:Cysteine / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D039121:Integrin alpha6beta1; D016023:Integrins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D007668:Kidney; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D051381:Rats; D017474:Receptors, Laminin / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013462:Sulfur Radioisotopes
D002135:Calcium-Binding Proteins; D039121:Integrin alpha6beta1; D016023:Integrins; D008565:Membrane Proteins; D017474:Receptors, Laminin; D013462:Sulfur Radioisotopes; D037281:Calnexin; D008715:Methionine; D003545:Cysteine