The laminin-binding activity of the alpha 7 integrin receptor is defined by developmentally regulated splicing in the extracellular domain.
The expression pattern of the laminin-binding alpha 7 beta 1 integrin is developmentally regulated in skeletal, cardiac, and smooth muscle. The X1/X2 alternative splicing in the extracellular domain of alpha 7 is found in the variable region between conserved alpha-chain homology repeat domains III and IV, a site implicated in ligand binding. To assess differences in X1/X2 isoform activity, we generated MCF-7 cell lines transfected with alpha 7-X1/X2 cDNAs. Transfectants expressing the alpha 7-X2 variant adhered rapidly to laminin 1, whereas those expressing alpha 7-X1 failed to attach. That alpha 7-X1 exists in an inactive state was established in assays using an activating beta 1 antibody that induced X1-dependent cell adhesion and spreading. Furthermore, the activation of alpha 7-X1 was cell type specific, and when expressed in HT1080 cells, the integrin was converted into a fully functional receptor capable of promoting adhesion. Thus, the expression of the alpha 7-X1/X2 integrin is a novel mechanism that regulates receptor affinity states in a cell-specific context and may modulate integrin-dependent events during muscle development and repair.
Ziober
B L
BL
Department of Stomatology, University of California, San Francisco 94143-0512, USA.
Chen
Y
Y
Kramer
R H
RH
D017398:Alternative Splicing; D001943:Breast Neoplasms; D002277:Carcinoma; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D007536:Isomerism; D007797:Laminin / Q000378:metabolism*; D008024:Ligands; D008345:Manganese / Q000494:pharmacology; D011485:Protein Binding; D017474:Receptors, Laminin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016023:Integrins; D007797:Laminin; D008024:Ligands; D017474:Receptors, Laminin; D008345:Manganese; C082908:integrin alpha7beta1