Loss of α1,6-fucosyltransferase decreases hippocampal long term potentiation: Implications for core fucosylation in the regulation of AMPA receptor heteromerization and cellular signaling

Wei Gu, Tomohiko Fukuda, Tomoya Isaji, Qinglei Hang, Ho Hsun Lee, Seiichiro Sakai, Jyoji Morise, Junya Mitoma, Hideyoshi Higashi, Naoyuki Taniguchi, Hiromu Yawo, Shogo Oka, Jianguo Gu

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    20 Citations (Scopus)

    Abstract

    Core fucosylation is catalyzed by α1,6-fucosyltransferase (FUT8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals. We previously reported that Fut8-knock-out (Fut8-/-) mice showed a schizophrenia-like phenotype and a decrease in working memory. To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. The scale of E-LTP induced by high frequency stimulation was significantly decreased in Fut8-/- mice. Tetraethylammonium-induced LTP showed no significant differences, suggesting that the decline in E-LTP was caused by postsynaptic events. Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8-/- mice. The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8-/- mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. The activation of AMPARs was further confirmed by Fura-2 calcium imaging using primary cultured neurons. Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-D-aspartate receptors as well as Ca2+ influx and CaMKII and then impair LTP.

    Original languageEnglish
    Pages (from-to)17566-17575
    Number of pages10
    JournalJournal of Biological Chemistry
    Volume290
    Issue number28
    DOIs
    Publication statusPublished - 2015 Jul 10

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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    Gu, W., Fukuda, T., Isaji, T., Hang, Q., Lee, H. H., Sakai, S., Morise, J., Mitoma, J., Higashi, H., Taniguchi, N., Yawo, H., Oka, S., & Gu, J. (2015). Loss of α1,6-fucosyltransferase decreases hippocampal long term potentiation: Implications for core fucosylation in the regulation of AMPA receptor heteromerization and cellular signaling. Journal of Biological Chemistry, 290(28), 17566-17575. https://doi.org/10.1074/jbc.M114.579938