Inositol Hexakisphosphate Kinase-2 in Cerebellar Granule Cells Regulates Purkinje Cells and Motor Coordination via Protein 4.1N

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Latika NagpalSolomon H Snyder

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.SIGNIFICANCE STATEMENT Inositol phosphates are produced by a family of inositol hexakisphosphate kinases (IP6Ks)-IP6K1, IP6K2, and I...Continue Reading

Citations

May 14, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Seulgi LeeSeyun Kim
Feb 7, 2021·Proceedings of the National Academy of Sciences of the United States of America·Latika NagpalSolomon H Snyder

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