title: Expression of alpha 7 integrin cytoplasmic domains during skeletal muscle development: alternate forms, conformational change, and homologies with serine/threonine kinases and tyrosine phosphatases.
abstract: We recently reported the cloning and sequencing of the alpha 7 integrin chain and its regulated expression during the development of skeletal muscle (Song et al. (1992) J. Cell Biol. 117, 643-657). The alpha 7 chain is expressed during the development of the myogenic lineage and on adult muscle fibers and this suggests that it participates in multiple and diverse functions at different times during muscle development. One interesting portion of this isoform is its cytoplasmic domain; comprised of 77 amino acids it is the largest in the alpha chains thus reported. In these experiments we begin to study the potential functions of the alpha 7 cytoplasmic domain by analyzing homologies between the rat and human sequences, by immunologic studies using an anti-cytoplasmic domain antiserum, and by identifying two alternate forms. In keeping with the nomenclature used to describe the alpha 3 and alpha 6 alternate cytoplasmic domains, we refer to the originally reported species as alpha 7B and the two additional forms as alpha 7A and alpha 7C. These three cytoplasmic domains likely arise as a consequence of alternate splicing. A splice site at the junctions of the transmembrane and cytoplasmic domains is used to generate the alpha 3, alpha 6 and alpha 7 A and B forms. The alpha 7A form RNA contains an additional 113 nucleotides compared to the B form, and a common coding region in the A and B form RNAs is used in alternate reading frames. Part of the coding region of alpha 7B appears to be used as the 3'-untranslated region of the alpha 7A form. The alpha 7C mRNA is 595 nucleotides smaller than the alpha 7B RNA and part of the 3'-untranslated region of the alpha 7B isoform is used as coding sequence in alpha 7C. There is developmental specificity in expression of these alternate mRNAs: alpha 7A and alpha 7C transcripts are found upon terminal myogenic differentiation whereas alpha 7B is present earlier in replicating cells and diminishes upon differentiation. We suggest this selective expression of the alpha 7 cytoplasmic domains underlies the diversity in function of the alpha 7 beta 1 integrin at different stages of muscle development. Immunochemical analyses indicate that the alpha 7B cytoplasmic domain undergoes a change in conformation in response to binding laminin or upon crosslinking initiated with antibody reactive with the integrin extracellular domain. Crosslinking also promotes association of the integrin with the cell cytoskeleton.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Cell and Structural Biology, University of Illinois, Urbana 61801.
authors.forename: W K
authors.initials: WK
authors.lastname: Song
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: D A
authors.initials: DA
authors.lastname: Bielser
authors.forename: S J
authors.initials: SJ
authors.lastname: Kaufman
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D002454:Cell Differentiation; D003432:Cross-Linking Reagents; D003599:Cytoskeleton / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D039001:Integrin alpha Chains; D016023:Integrins / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D009132:Muscles / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship
chemical_list: D015703:Antigens, CD; D003432:Cross-Linking Reagents; D039001:Integrin alpha Chains; D016023:Integrins; D012333:RNA, Messenger; C085725:integrin alpha7; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases