title: Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING.
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 Ca(2+) influx and CaMKII and then impair LTP.
authors.affiliation: From the Division of Regulatory Glycobiology and.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: From the Division of Regulatory Glycobiology and.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: From the Division of Regulatory Glycobiology and.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Isaji
authors.affiliation: From the Division of Regulatory Glycobiology and.
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Hang
authors.affiliation: From the Division of Regulatory Glycobiology and.
authors.forename: Ho-hsun
authors.initials: HH
authors.lastname: Lee
authors.affiliation: the Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, 980-8577.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Sakai
authors.affiliation: the Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, and.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Morise
authors.affiliation: the Division of Glyco-Signal Research, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558.
authors.forename: Junya
authors.initials: J
authors.lastname: Mitoma
authors.affiliation: the Division of Glyco-Signal Research, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Higashi
authors.affiliation: the Disease Glycomics Team, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.affiliation: the Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, 980-8577.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Yawo
authors.affiliation: the Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, and.
authors.forename: Shogo
authors.initials: S
authors.lastname: Oka
authors.affiliation: From the Division of Regulatory Glycobiology and jgu@tohoku-pharm.ac.jp.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D005260:Female; D005643:Fucose / Q000378:metabolism; D005647:Fucosyltransferases / Q000172:deficiency* / Q000235:genetics; D006031:Glycosylation; D006624:Hippocampus / Q000502:physiology*; D007858:Learning / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008568:Memory / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D055503:Protein Multimerization; D018091:Receptors, AMPA / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D009435:Synaptic Transmission
chemical_list: D018091:Receptors, AMPA; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: N-linked glycosylation; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR); fucosyltransferase; glycobiology; glycosylation; schizophrenia