A novel isoform of the mitochondrial outer membrane protein VDAC3 via alternative splicing of a 3-base exon. Functional characteristics and subcellular localization.
Voltage-dependent anion channels (VDACs) are pore-forming proteins found in the outer mitochondrial membrane of all eucaryotes. VDACs are the major pathway for metabolites through the outer mitochondrial membrane and, in mammals, bind several cytosolic carbohydrate kinases. Whereas yeast contain a single VDAC (YVDAC), to date three isoforms have been described in the mouse that constitute a gene family. We have observed an additional isoform of VDAC3 that appears to be generated via the tissue-specific alternative splicing of a 3-base exon (ATG). The exon is predicted to introduce a methionine 39 amino acids downstream of the amino terminus of the polypeptide. Between exons 3 and 4 is an intronic sequence that potentially encodes the exon, with flanking splice enhancer elements. Expression of this alternative form in the mouse is limited to brain, heart, and skeletal muscle. Complementation of YVDAC-deficient yeast by the two isoforms and with other sequence variants of VDAC3 suggests this residue is an important modulator of VDAC3 function. In transfected mammalian cells both isoforms localize to mitochondria. A similar variant is present in humans.
Sampson
M J
MJ
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Ross
L
L
Decker
W K
WK
Craigen
W J
WJ
D016475:3T3 Cells; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D005091:Exons; D005455:Fluorescent Antibody Technique; D007438:Introns; D007473:Ion Channels / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008928:Mitochondria / Q000737:chemistry*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D018272:Porins; D050994:Voltage-Dependent Anion Channels
D007473:Ion Channels; D008565:Membrane Proteins; D018272:Porins; D050994:Voltage-Dependent Anion Channels