Characterization of a valproic acid-sensitive mutant allele of the Golgi GDP-mannose transmembrane transporter Vrg4 in Schizosaccharomyces pombe.

Abstract

Valproic acid (VPA) is a widely used drug for epilepsy. However, precise molecular mechanisms relevant to VPA's side effects remain elusive. This study identifies a VPA-sensitive mutant strain ( vas21 ) in fission yeast with a missense mutation (T256I) in the nucleotide sugar-binding motif of the GDP-mannose transporter Vrg4 . This mutation impairs protein glycosylation, as evidenced by altered acid phosphatase mobility. We also found that Vrg4 overexpression deteriorates cell growth. Our results highlight the role of Vrg4 in glycosylation and implicate impaired glycosylation as a potential mechanism underlying VPA sensitivity. The new allele of vrg4 will be useful in glycobiology and pharmacology.