title: Involvement of afadin in the formation and remodeling of synapses in the hippocampus.
abstract: In the hippocampus, synapses are formed between mossy fiber terminals and CA3 pyramidal cell dendrites and comprise highly developed synaptic junctions (SJs) and puncta adherentia junctions (PAJs). Dynamic remodeling of synapses in the hippocampus is implicated in learning and memory. Components of both the nectin-afadin and cadherin-catenin cell adhesion systems exclusively accumulate at PAJs. We investigated the role of afadin at synapses in mice in which the afadin gene was conditionally inactivated in hippocampal neurons. In these mutant mice, the signals for not only nectins, but also N-cadherin and beta-catenin, were hardly detected in the CA3 area, in addition to loss of the signal for afadin, resulting in disruption of PAJs. Ultrastructural analysis revealed an increase in the number of perforated synapses, suggesting the instability of SJs. These results indicate that afadin is involved not only in the assembly of nectins and cadherins at synapses, but also in synaptic remodeling.
authors.affiliation: Department of Biochemistry, Osaka University Graduate School of Medicine, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Majima
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ogita
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Amano
authors.forename: Hideru
authors.initials: H
authors.lastname: Togashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sakisaka
authors.forename: Miki
authors.initials: M
authors.lastname: Tanaka-Okamoto
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ishizaki
authors.forename: Jun
authors.initials: J
authors.lastname: Miyoshi
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D000075983:Nectins; D017966:Pyramidal Cells / Q000201:enzymology / Q000648:ultrastructure; D013569:Synapses / Q000201:enzymology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D000075983:Nectins; C108835:afadin; D051176:beta Catenin; D011495:Histone-Lysine N-Methyltransferase; C516439:MLL4 protein, mouse