Identification of a novel CoA synthase isoform, which is primarily expressed in the brain

• Published in: Biochemical and biophysical research communications Vol. 341; no. 4; pp. 995 - 1000
• Main Authors: Nemazanyy, Ivan, Panasyuk, Ganna, Breus, Oksana, Zhyvoloup, Alexander, Filonenko, Valeriy, Gout, Ivan T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.03.2006
• Subjects: 60 APPLIED LIFE SCIENCES; Alternative Splicing; Amino Acid Sequence; Animals; ANTIBODIES; BIOSYNTHESIS; BRAIN; Brain - enzymology; CLONING; CoASy α; CoASy β; Coenzyme A; Coenzyme A synthase; COENZYMES; COMPLEXES; ENZYMES; Humans; Isoenzymes - biosynthesis; METABOLISM; Mice; MICROSCOPY; MITOCHONDRIA; Mitochondria - enzymology; Molecular Sequence Data; NIH 3T3 Cells; PEPTIDES; POLYMERASE CHAIN REACTION; Protein isoform; RATS; Reverse Transcriptase Polymerase Chain Reaction; Sequence Alignment; Splice variant; SPLICING; Transferases - biosynthesis; Coenzyme A synthase; Coenzyme A; Splice variant; CoASy α; CoASy β; Protein isoform
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.01.051

CoA and its derivatives Acetyl-CoA and Acyl-CoA are important players in cellular metabolism and signal transduction. CoA synthase is a bifunctional enzyme which mediates the final stages of CoA biosynthesis. In previous studies, we have reported molecular cloning, biochemical characterization, and subcellular localization of CoA synthase (CoASy). Here, we describe the existence of a novel CoA synthase isoform, which is the product of alternative splicing and possesses a 29aa extension at the N-terminus. We termed it CoASy β and originally identified CoA synthase, CoASy α. The transcript specific for CoASy β was identified by electronic screening and by RT-PCR analysis of various rat tissues. The existence of this novel isoform was further confirmed by immunoblot analysis with antibodies directed to the N-terminal peptide of CoASy β. In contrast to CoASy α, which shows ubiquitous expression, CoASy β is primarily expressed in the brain. Using confocal microscopy, we demonstrated that both isoforms are localized on mitochondria. The N-terminal extension does not affect the activity of CoA synthase, but possesses a proline-rich sequence which can bring the enzyme into complexes with signalling proteins containing SH3 or WW domains. The role of this novel isoform in CoA biosynthesis, especially in the brain, requires further elucidation.