Alternative splicing of GAD67 results in the synthesis of a third form of glutamic-acid decarboxylase in human islets and other non-neural tissues

J Biol Chem. 2000 Feb 18;275(7):5188-92. doi: 10.1074/jbc.275.7.5188.

Abstract

Two forms of glutamic-acid decarboxylase (GAD) have been identified in mammalian tissues: a 65-kDa form (GAD65) and a 67-kDa form (GAD67). Alternate splicing produces one or two smaller variants of GAD67 in the brain of embryonic mice and rats. Additionally, a short, heretofore unidentified transcript homologous to GAD67 has been detected in human testis RNA. Because GAD, the enzyme responsible for gamma-aminobutyric acid production and a key autoantigen in type I diabetes, has unclear function in non-neural tissue, it is important to understand its pattern of expression. Unlike GAD65, GAD67 is not produced in human pancreatic islets. Here, we describe a novel splice variant of GAD67 that is produced in human islets, testis, adrenal cortex, and perhaps other endocrine tissues, but not in brain. This transcript directs the synthesis of a protein without GAD enzymatic activity: GAD25. A unique peptide sequence at the carboxyl terminus of GAD25 is highly conserved between mice, rats, and humans. We conclude that humans produce a third form of GAD in non-neural tissues and that human islets, although they do not synthesize full-length GAD67, do express this shortened variant.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing*
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • DNA, Complementary
  • Glutamate Decarboxylase / biosynthesis
  • Glutamate Decarboxylase / genetics*
  • Humans
  • Islets of Langerhans / enzymology*
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics*
  • Male
  • Molecular Sequence Data
  • Sequence Homology, Nucleic Acid
  • Testis / enzymology*

Substances

  • DNA, Complementary
  • Isoenzymes
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1

Associated data

  • GENBANK/AF178853