title: Dendritic spine formation and synaptic function require neurobeachin.
abstract: A challenge in neuroscience is to understand the mechanisms underlying synapse                 formation. Most excitatory synapses in the brain are built on spines, which are                 actin-rich protrusions from dendrites. Spines are a major substrate of brain                 plasticity, and spine pathologies are observed in various mental illnesses. Here we                 investigate the role of neurobeachin (Nbea), a multidomain protein previously linked                 to cases of autism, in synaptogenesis. We show that deletion of Nbea leads to                 reduced numbers of spinous synapses in cultured neurons from complete knockouts and                 in cortical tissue from heterozygous mice, accompanied by altered miniature                 postsynaptic currents. In addition, excitatory synapses terminate mostly at                 dendritic shafts instead of spine heads in Nbea mutants, and actin becomes less                 enriched synaptically. As actin and synaptopodin, a spine-associated protein with                 actin-bundling activity, accumulate ectopically near the Golgi apparatus of mutant                 neurons, a role emerges for Nbea in trafficking important cargo to pre- and                 postsynaptic compartments.
authors: Department of Anatomy and Molecular Neurobiology, Westfälische Wilhelms-University, Münster 48149, Germany.
authors: Katharina
authors: K
authors: Niesmann
authors: Dorothee
authors: D
authors: Breuer
authors: Johannes
authors: J
authors: Brockhaus
authors: Gesche
authors: G
authors: Born
authors: Ilka
authors: I
authors: Wolff
authors: Carsten
authors: C
authors: Reissner
authors: Manfred W
authors: MW
authors: Kilimann
authors: Astrid
authors: A
authors: Rohlmann
authors: Markus
authors: M
authors: Missler
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism*; D004594:Electrophysiology; D007150:Immunohistochemistry; D008565:Membrane Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D000199:Actins; D002352:Carrier Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C403265:Nbea protein, mouse; D009419:Nerve Tissue Proteins; C503968:Synpo protein, mouse