Importin α5 Regulates Anxiety through MeCP2 and Sphingosine Kinase 1

Nicolas Panayotis, Anton Sheinin, Shachar Y. Dagan, Michael M. Tsoory, Franziska Rother, Mayur Vadhvani, Anna Meshcheriakova, Sandip Koley, Letizia Marvaldi, Didi-Andreas Song, Eitan Reuveny, Britta J. Eickholt, Enno Hartmann, Michael Bader, Izhak Michaelevski, Mike Fainzilber

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

תקציר

Importins mediate transport from synapse to soma and from cytoplasm to nucleus, suggesting that perturbation of importin-dependent pathways should have significant neuronal consequences. A behavioral screen on five importin α knockout lines revealed that reduced expression of importin α5 (KPNA1) in hippocampal neurons specifically decreases anxiety in mice. Re-expression of importin α5 in ventral hippocampus of knockout animals increased anxiety behaviors to wild-type levels. Hippocampal neurons lacking importin α5 reveal changes in presynaptic plasticity and modified expression of MeCP2-regulated genes, including sphingosine kinase 1 (Sphk1). Knockout of importin α5, but not importin α3 or α4, reduces MeCP2 nuclear localization in hippocampal neurons. A Sphk1 blocker reverses anxiolysis in the importin α5 knockout mouse, while pharmacological activation of sphingosine signaling has robust anxiolytic effects in wild-type animals. Thus, importin α5 influences sphingosine-sensitive anxiety pathways by regulating MeCP2 nuclear import in hippocampal neurons. Panayotis et al. found decreased anxiety in importin α5 knockout mice. They report that importin α5 influences sphingosine-sensitive anxiety pathways by regulating MeCP2 nuclear import in hippocampal neurons.

שפה מקוריתאנגלית
עמודים (מ-עד)3169-3179.e7
מספר עמודים18
כתב עתCell Reports
כרך25
מספר גיליון11
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 11 דצמ׳ 2018

ASJC Scopus subject areas

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