The beta1 cytoplasmic domain regulates the laminin-binding specificity of the alpha7X1 integrin.
During muscle development, the laminin-specific alpha7 integrin is alternatively spliced in the putative ligand-binding domain to yield either the alpha7X1 or the alpha7X2 variant. The relative level of alpha7X1 and alpha7X2 is developmentally regulated. Similarly, the partner beta1 integrin cytoplasmic domain is converted from the beta1A to the beta1D splice variant. To determine whether beta1D modulates the activity of the alpha7 receptor, cells were transfected with alpha7X1 and beta1D cDNA. alpha7X1 coupled with beta1A failed to adhere to laminin-1, whereas cotransfectants expressing alpha7X1 and beta1D showed strong adhesion. Interestingly, alpha7X1 complexed with beta1A and beta1D displayed the same level of poor adhesion to laminin-2/4 or strong adhesion to laminin-10/11. These findings indicate that alpha7 function is regulated not only by X1/X2 in its extracellular domain but also by beta1 cytoplasmic splice variants. It is likely that expression of beta1D alters alpha7X1 binding to laminin isoforms by a process related to ligand affinity modulation. Functional regulation of alpha7beta1 by developmentally regulated splicing events may be important during myogenic differentiation and repair because the integrin mediates adhesion, motility, and cell survival.
Yeh
Ming-Guang
MG
Department of Stomatology, University of California at San Francisco, San Francisco, CA 94143-0512, USA.
Ziober
Barry L
BL
Liu
Baomei
B
Lipkina
Galina
G
Vizirianakis
Ioannis S
IS
Kramer
Randall H
RH
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D003001:Cloning, Molecular; D005434:Flow Cytometry; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism*; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000502:physiology*; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics; D021122:Protein Subunits / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D002352:Carrier Proteins; D039001:Integrin alpha Chains; D019012:Integrin beta1; D007797:Laminin; D020033:Protein Isoforms; D021122:Protein Subunits; C085725:integrin alpha7