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Functional Regulation of Alternatively Spliced Na + /Ca 2+ Exchanger (NCX1) Isoforms
Author(s) -
SCHULZE D. H.,
POLUMURI S. K.,
GILLE T.,
RUKNUDIN A.
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04740.x
Subject(s) - exon , gene isoform , alternative splicing , microbiology and biotechnology , gene , biology , rna splicing , messenger rna , gene expression , rna , genetics
A bstract : Alternative splicing of RNA transcripts is a general characteristic for NCX genes in mammals, mollusks, and arthropods. Among the family of three NCX genes in mammals, the NCX1 gene contains six exons, namely, A, B, C, D, E, and F, that make up the alternatively spliced region. Studies of the NCX1 gene transcripts suggested that 16 distinct gene products can be produced from the NCX1 gene. The exons A and B are mutually exclusive when expressed. Generally, exon A‐containing transcripts are predominantly found in excitable cells like cardiomyoctes and neurons, whereas exon B‐containing transcripts are mostly found in nonexcitable cells like astrocytes and kidney cells. Other alternatively spliced exons (C‐F) appear to be cassette‐type exons and are found in various combinations. Interestingly, exon D is present in all characterized transcripts. The alternatively spliced isoforms of NCX1 show tissue‐specific expression patterns, suggesting functional adaptation to tissues. To investigate functional differences among alternatively spliced isoforms of NCX1, we expressed an exon A‐containing transcript present in cardiac tissue (NCX1.1) and an exon B‐containing transcript found in the kidney (NCX1.3) in Xenopus oocytes. We demonstrated that the Na + /Ca 2+ exchangers expressed by exon A‐ and exon B‐containing transcripts display differences in activation by PKA and by [Ca 2+ ] i . We also observed that these two isoforms show differences in voltage dependence. Suprisingly, the alternatively spliced isoforms of NCX1 display greater functional differences among themselves than the products of different gene loci, NCX1, NCX2, and NCX3.