Inositol hexakisphosphate kinase-2 in cerebellar granule cells regulates Purkinje cells and motor coordination via protein 4.1N

Latika Nagpal, Chenglai Fu, Solomon H Snyder

Research output: Contribution to journalArticle

Abstract

Inositol hexakisphosphate kinases (IP6Ks) regulate various biological processes. Among pyrophosphates generated by IP6Ks, diphosphoinositol pentakisphosphate (IP7), and bis-diphosphoinositol tetrakisphosphate have been extensively characterized. IP7 is produced in mammals by a family of inositol hexakisphosphate kinases, IP6K1, IP6K2, and IP6K3, which have distinct biological functions. We report that IP6K2 binds protein 4.1.N with high affinity and specificity. Nuclear translocation of 4.1N, which is required for its principal functions, is dependent on IP6K2. Both of these proteins are highly expressed in granule cells of the cerebellum where their interaction regulates Purkinje cell morphology and cerebellar synapses. The deletion of IP6K2 in male/female mice elicits substantial defects in synaptic influences of granule cells upon Purkinje cells as well as notable impairment of locomotor function. Moreover, the disruption of IP6K2–4.1N interactions impairs cell viability. Thus, IP6K2 and its interaction with 4.1N appear to be major determinants of cerebellar disposition and psychomotor behavior.

Original languageEnglish (US)
Pages (from-to)7409-7419
Number of pages11
JournalJournal of Neuroscience
Volume38
Issue number34
DOIs
StatePublished - Aug 22 2018

Keywords

  • 4.1N
  • Cerebellum
  • IP6K2
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)

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