Inositol hexakisphosphate kinase-1 regulates behavioral responses via GSK3 signaling pathways

A. Chakraborty, C. Latapy, J. Xu, S. H. Snyder, J. M. Beaulieu

Research output: Contribution to journalArticlepeer-review

Abstract

Glycogen synthase kinase 3 (GSK3), a prominent enzyme in carbohydrate metabolism, also has a major role in brain function. It is physiologically regulated by the kinase Akt, which phosphorylates GSK3 to inhibit catalytic activity. Inositol hexakisphosphate-1 (IP6K1) generates the inositol pyrophosphate diphosphoinositol pentakisphosphate (IP7), which physiologically inhibits Akt leading to enhanced GSK3 activity. We report that IP6K1 binds and stimulates GSK3 enzymatic activity in a non-catalytic fashion. Physiological relevance is evident in the inhibition of GSK3 activity in the brains of IP6K1-deleted mice. Behavioral alterations of IP6K1 knockout mice resemble those of GSK3 mutants. Accordingly, modulation of IP6K1-GSK3β interaction may exert beneficial effects in psychiatric disorders involving GSK3.

Original languageEnglish (US)
Pages (from-to)284-293
Number of pages10
JournalMolecular psychiatry
Volume19
Issue number3
DOIs
StatePublished - Mar 2014

Keywords

  • Behavior
  • GSK3
  • IP6K1

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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