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Article Dans Une Revue Cell Reports Année : 2018

Importin α5 Regulates Anxiety through MeCP2 and Sphingosine Kinase 1

Résumé

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.
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hal-03506480 , version 1 (02-01-2022)

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Nicolas Panayotis, Anton Sheinin, Shachar y Dagan, Michael M Tsoory, Franziska Rother, et al.. Importin α5 Regulates Anxiety through MeCP2 and Sphingosine Kinase 1. Cell Reports, 2018, 25 (11), pp.3169-3179.e7. ⟨10.1016/j.celrep.2018.11.066⟩. ⟨hal-03506480⟩
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