Expression of α7 integrin cytoplasmic domains during skeletal muscle development: alternate forms, conformational change, and homologies with serine/threonine kinases and tyrosine phosphatases
Authors: Song Woo Keun , Wang Weigwang , Sato Hiroyuki , Bielser Deborah A. , Kaufman Stephen J. 
Published: April 2021

ABSTRACT
We recently reported the cloning and sequencing of the7 integrin chain and its regulated expression during the development of skeletal muscle (Song et al. (1992)J. Cell Biol. 117, 643-657). The 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 7 cytoplasmic domain by ana-lyzing homologies between the rat and human sequences, by immunologic studies using an anti-cyto-plasmic domain antiserum, and by identifying two alternate forms. In keeping with the nomenclature used to describe the 3 and 6 alternate cytoplasmic domains, we refer to the originally reported species as 7B and the two additional forms as 7A and 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 gen-erate the 3, 6 and 7 A and B forms. The 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 7B appears to be used as the 3-untranslated region of the 7A form. The 7C mRNA is 595 nucleotides smaller than the 7B RNA and part of the 3-untranslated region of the 7B isoform is used as coding sequence in 7C. There is developmental specificity in expression of these alternate mRNAs: 7A and 7C transcripts are found upon terminal myogenic differentiation whereas 7B is present earlier in replicating cells and diminishes upon differentiation. We suggest this selective expression of the 7 cytoplasmic domains underlies the diversity in function of the 7 1 integrin at different stages of muscle development.
Immunochemical analyses indicate that the 7B cytoplasmic domain undergoes a change in conformation in response to binding laminin or upon crosslinking initiated with antibody reactive with the integrin extracel-lular domain. Crosslinking also promotes association of the integrin with the cell cytoskeleton. Analysis of the amino acid sequence of the 7B cytoplasmic domain reveals several motifs that may relate to the function of this protein. Two regions in the 7B cytoplasmic domain have homology and similar apposition to those in the catalytic phosphotransfer domain and the ATP-binding site of serine/threonine protein kinases. There is also a sequence of 15 amino acids in the 7B cytoplasmic domain that is homologous to that in many receptor-like protein tyrosine phosphatases. Although this cytoplasmic domain may be too small to have catalytic properties, it may effect the localization or regulation of these enzymes, or other proteins that interact with them. There is also a potential actin-binding sequence and a unique three-fold DXHPX repeat towards the carboxyl end of the 7B cytoplasmic domain. Clearly, the 7B cytoplasmic domain contains a rich potential for par-ticipating in the transduction of signals initiated outside the cell. This diversity in features, conformational changes, and forms of the 7 cytoplasmic domains likely underlie its diverse functions on skeletal muscle.