title: Neurobeachin regulates neurotransmitter receptor trafficking to synapses.
abstract: The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found that neurons lacking the BEACH (beige-Chediak/Higashi) domain protein Neurobeachin (Nbea) had strongly reduced synaptic responses caused by a reduction in surface levels of glutamate and GABA(A) receptors. In the absence of Nbea, immature AMPA receptors accumulated early in the biosynthetic pathway, and mature N-methyl-d-aspartate, kainate, and GABA(A) receptors did not reach the synapse, whereas maturation and surface expression of other membrane proteins, synapse formation, and presynaptic function were unaffected. These data show that Nbea regulates synaptic transmission under basal conditions by targeting neurotransmitter receptors to synapses.
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Ramya
authors.initials: R
authors.lastname: Nair
authors.forename: Juliane
authors.initials: J
authors.lastname: Lauks
authors.forename: SangYong
authors.initials: S
authors.lastname: Jung
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Cooke
authors.forename: Heidi
authors.initials: H
authors.lastname: de Wit
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Manfred W
authors.initials: MW
authors.lastname: Kilimann
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
authors.forename: JeongSeop
authors.initials: J
authors.lastname: Rhee
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C403265:Nbea protein, mouse