Identification of a novel signaling pathway and its relevance for GluA1 recycling

  • We previously showed that the serum- and glucocorticoid-inducible kinase 3 (SGK3) increases the AMPA-type glutamate receptor GluA1 protein in the plasma membrane. The activation of AMPA receptors by NMDA-type glutamate receptors eventually leads to postsynaptic neuronal plasticity. Here, we show that SGK3 mRNA is upregulated in the hippocampus of new-born wild type Wistar rats after NMDA receptor activation. We further demonstrate in the \(\it Xenopus\) oocyte expression system that delivery of GluA1 protein to the plasma membrane depends on the small GTPase RAB11. This RAB-dependent GluA1 trafficking requires phosphorylation and activation of phosphoinositol-3-phosphate-5-kinase (PIKfyve) and the generation of \(PI(3,5)P_{2}\). In line with this mechanism we could show PIKfyve mRNA expression in the hippocampus of wild type C57/BL6 mice and phosphorylation of PIKfyve by SGK3. Incubation of hippocampal slices with the PIKfyve inhibitor YM201636 revealed reduced CA1 basal synaptic activity. Furthermore, treatment of primary hippocampal neurons with YM201636 altered the GluA1 expression pattern towards reduced synaptic expression of GluA1. Our findings demonstrate for the first time an involvement of PIKfyve and \(PI(3,5)P_{2}\) in NMDA receptor-triggered synaptic GluA1 trafficking. This new regulatory pathway of GluA1 may contribute to synaptic plasticity and memory.

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Author:Guiscard Friedrich Aldous SeebohmGND, Sebastian NeumannORCiDGND, Carsten TheißORCiDGND, Tanja NovkovicGND, Elaine V. HillGND, Jeremy M. TavaréGND, Florian LangGND, Michael HollmannORCiDGND, Denise Manahan-VaughanORCiDGND, Nathalie Strutz-SeebohmGND
URN:urn:nbn:de:hbz:294-72806
DOI:https://doi.org/10.1371/journal.pone.0033889
Parent Title (English):PLoS ONE
Publisher:Public Library of Science
Place of publication:San Francisco
Document Type:Article
Language:English
Date of Publication (online):2020/07/03
Date of first Publication:2012/03/21
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Volume:7
Issue:3, Artikel e33889
First Page:e33889-1
Last Page:e33889-10
Institutes/Facilities:Lehrstuhl Biochemie I, Rezeptorbiochemie
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International