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| Item Type: | Article |
|---|---|
| Title: | Importin α5 regulates anxiety through MeCP2 and sphingosine kinase 1 |
| Creators Name: | Panayotis, N., Sheinin, A., Dagan, S.Y., Tsoory, M.M., Rother, F., Vadhvani, M., Meshcheriakova, A., Koley, S., Marvaldi, L., Song, D.A., Reuveny, E., Eickholt, B.J., Hartmann, E., Bader, M., 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 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 25 |
| Number: | 11 |
| 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 |
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