A new isoform of the laminin receptor integrin alpha 7 beta 1 is developmentally regulated in skeletal muscle.
Within the integrin family, there are two groups of receptors that bind laminin. One of these groups comprises the heterodimers alpha 3 beta 1, alpha 6 beta 1, and alpha 7 beta 1, all of which bind the E8 fragment of laminin, and whose alpha subunits show significant homology at the amino acid sequence level. alpha 3 and alpha 6 exist as isoforms with distinct cytoplasmic domains (termed A and B), suggesting that they may couple laminin adhesion to distinct cellular responses. We report the identification of a new alpha 7 mRNA which encodes an alpha 7 protein isoform with an alternative cytoplasmic domain. Based on homology with alpha 3 and alpha 6 isoforms, this new isoform is classified as alpha 7A and the previously published one as alpha 7B. This result extends the similarity between alpha 3, alpha 6, and alpha 7 laminin receptor subunits and suggests a common ancestral gene. The alpha 7 beta 1 laminin receptor was proposed to be involved in myogenic differentiation. However, alpha 7 isoforms were not investigated in that context. We detected the alpha 7B isoform mRNA in all tissues and cell types tested, including myocardial and skeletal muscle. In contrast, the alpha 7A isoform was detectable exclusively in skeletal muscle, not in myocardial muscle or cells or any other tissues or cell lines tested. Furthermore, the differentiating skeletal muscle cell line C2C12 expressed only alpha 7B at the replicating myoblast stage and acquired alpha 7A expression upon induction of differentiation and fusion. Splicing of alpha 7B mRNA in C2C12 occurred shortly after myogenin expression and could be an indicator of progression through the program of skeletal muscle differentiation.
Collo
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Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037.
Starr
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Quaranta
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D005260:Female; D005786:Gene Expression Regulation; D016023:Integrins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D024510:Muscle Development; D009132:Muscles / Q000737:chemistry / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D016023:Integrins; D007797:Laminin; D012333:RNA, Messenger; C082908:integrin alpha7beta1