Helmholtz Gemeinschaft


Importin α5 regulates anxiety through MeCP2 and sphingosine kinase 1

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplemental Information)

Item Type:Article
Title:Importin α5 regulates anxiety through MeCP2 and sphingosine kinase 1
Creators Name:Panayotis, N. and Sheinin, A. and Dagan, S.Y. and Tsoory, M.M. and Rother, F. and Vadhvani, M. and Meshcheriakova, A. and Koley, S. and Marvaldi, L. and Song, D.A. and Reuveny, E. and Eickholt, B.J. and Hartmann, E. and Bader, M. and Michaelevski, I. and Fainzilber, M.
Abstract: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.
Keywords:Anxiety, Anxiolytic, Importin, Karyopherin, KPNA1, MeCP2, Sphingosine Kinase, Synapse-Nucleus Communication, Animals, Mice
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:3169-3179
Date:11 December 2018
Official Publication:https://doi.org/10.1016/j.celrep.2018.11.066
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library