Developmental regulation of the alpha(7) integrin chain during myogenesis
Wang, Weigwang
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Permalink
https://hdl.handle.net/2142/19525
Description
Title
Developmental regulation of the alpha(7) integrin chain during myogenesis
Author(s)
Wang, Weigwang
Issue Date
1995
Doctoral Committee Chair(s)
Kaufman, Stephen J.
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Genetics
Biology, Cell
Language
eng
Abstract
The $\alpha$7$\beta$1 integrin is the major laminin receptor on skeletal muscle cells. Its expression is developmental regulated during myogenesis. Not only is the expression of $\alpha$7 transcripts increased upon myogenic differentiation, differential splicing of transcripts is also observed at that time. This differential splicing of $\alpha$7 transcripts results in three different mRNAs which encode $\alpha$7 chains with three different cytoplasmic domains. The $\alpha$7B form is expressed both in replicating myoblasts and in differentiated myotubes and adult fibers. The $\alpha$7A and $\alpha$7C forms are only detected after myoblasts have undergone terminal differentiation. These three isoforms contain both a common as well as distinct potential phosphorylation sites and these may function in alternate signal transduction events.
Analysis of chromosomal localization of the $\alpha$7 integrin gene (ITGA7) indicates that there is only one ITGA7 in the mammalian genome. ITGA7 is located on human chromosome 12q13. Phylogenetic analysis of integrin alpha chain genes show that the integrin genes evolved early into two pathways. The I-integrin genes are clustered on human chromosomes 5 and 16 and evolved by duplications within the same chromosome. The non-I-integrin genes are clustered on human chromosomes 2, 12 and 17. They appear to have evolved in concert with the two chromosome duplications that resulted in the expansion of the family of Hox genes.
To study the function of $\alpha$7 cytoplasmic domains, I constructed cDNA expression vectors encoding the three different cytoplasmic domains and a deletion mutation without the $\alpha$7 cytoplasmic domain. I determined that $\alpha$7 cytoplasmic domain is not necessary for integrin localization at the cell surface membrane and association with the cell cytoskeleton since cells transfected with the deletion mutant produced $\alpha$7 that could be detected on the cell surface and can associated with cell cytoskeleton.
Finally, I examined the effect of SV40 T antigen and 10T1/2 fibroblast culture medium on myoblast differentiation. Expression of SV40 T antigen inhibits terminal differentiation and it also inhibits the expression of the myoregulatory genes MyoD and myogenin. 10T1/2 fibroblasts, but not myoblasts derived from 10T1/2 cells, synthesize and secrete a substance that inhibits the differentiation of L8E63 myoblasts.
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