HUMAN BRAIN T CALCIUM CHANNEL ALPHA-SUBUNIT SPLICE VARIANTS

摘要

The structures of CACNA1G and CACNA1I, the genes encoding the human brain T Ca<2+> channel alpha 1G and alpha 1I subunits, respectively, were determined by comparison of polymerase chain reaction-amplified brain cDNA and genomic sequences. CACNA1G consists of at least 38 exons spanning at least 66,490 basepairs of chromosome 17q22. Alternative splicing of the RNA occurs at six sites: cassette exons 14, 26, 34 and 35, an internal donor in exon 25 and protein-coding intron 38B. Additionally, the RNA can be polyadenylated at either of two sites. Alternative splicing of CANCA1G RNA may lead to expression of as many as 64 distinct protein products, ranging from 2,171 to 2,377 amino-acids residues, with as many as 45 potential phosphorylation sites. CACNA1I consists of at least 37 exons spanning at least 116,390 basepairs of chromosome 22q12.3-13.2. Alternative splicing of the gene occurs at three sites: cassette exon 9, an alternative acceptor in exon 33 and mutually-exclusive 3' exons 36B and 37. Alternative splicing of CANCA1I RNA may lead to expression of as many as 8 distinct protein products, ranging from 1,968 to 2,223 amino-acids residues, with as many as 28 potential phosphorylation sites. Molecular diversity generated by alternative splicing and post-translation modification of these and other members of the T alpha 1 subunit gene family may account for the observed heterogeneity of T currents in central neurons.