title: Dlg5 regulates dendritic spine formation and synaptogenesis by controlling subcellular N-cadherin localization.
abstract: Most excitatory synapses in the mammalian brain are formed on dendritic spines, and spine density has a profound impact on synaptic transmission, integration, and plasticity. Membrane-associated guanylate kinase (MAGUK) proteins are intracellular scaffolding proteins with well established roles in synapse function. However, whether MAGUK proteins are required for the formation of dendritic spines in vivo is unclear. We isolated a novel disc large-5 (Dlg5) allele in mice, Dlg5(LP), which harbors a missense mutation in the DLG5 SH3 domain, greatly attenuating its ability to interact with the DLG5 GUK domain. We show here that DLG5 is a MAGUK protein that regulates spine formation, synaptogenesis, and synaptic transmission in cortical neurons. DLG5 regulates synaptogenesis by enhancing the cell surface localization of N-cadherin, revealing a key molecular mechanism for regulating the subcellular localization of this cell adhesion molecule during synaptogenesis.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Shih-Hsiu J
authors.initials: SH
authors.lastname: Wang
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Ivana
authors.initials: I
authors.lastname: Celic
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, Department of Physiology, Seoul National University School of Dentistry, Seoul, Korea, 110-749, and.
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Martin
authors.initials: M
authors.lastname: Riccomagno
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Lu O
authors.initials: LO
authors.lastname: Sun
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Mitchell
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer research Center, Seattle, Washington 98109.
authors.forename: Valera
authors.initials: V
authors.lastname: Vasioukhin
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, kolodkin@jhmi.edu.
authors.forename: Alex L
authors.initials: AL
authors.lastname: Kolodkin
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology / Q000648:ultrastructure; D049229:Dendritic Spines / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D051528:Guanylate Kinases / Q000235:genetics / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020125:Mutation, Missense; D055495:Neurogenesis / Q000502:physiology*; D061251:Primary Cell Culture; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D008565:Membrane Proteins; D051176:beta Catenin; C523873:Dlg5 protein, mouse; D051528:Guanylate Kinases
keywords: Dlg5; N-cadherin; dendritic spine; synaptogenesis