title: Neurobeachin is essential for neuromuscular synaptic transmission.
abstract: We report a random disruption in the mouse genome that resulted in lethal paralysis in homozygous newborns. The disruption blocked expression of neurobeachin, a protein containing a BEACH (beige and Chediak-Higashi) domain implicated in synaptic vesicle trafficking and an AKAP (A-kinase anchor protein) domain linked to localization of cAMP-dependent protein kinase activity. nbea-null mice demonstrated a complete block of evoked synaptic transmission at neuromuscular junctions, whereas nerve conduction, synaptic structure, and spontaneous synaptic vesicle release were completely normal. These findings support an essential role for neurobeachin in evoked neurotransmitter release at neuromuscular junctions and suggest that it plays an important role in synaptic transmission.
authors.affiliation: Department of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Su
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Balice-Gordon
authors.forename: Darren M
authors.initials: DM
authors.lastname: Hess
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Landsman
authors.forename: Jeremy
authors.initials: J
authors.lastname: Minarcik
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Golden
authors.forename: Ivy
authors.initials: I
authors.lastname: Hurwitz
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Liebhaber
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Cooke
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D002478:Cells, Cultured; D004392:Dwarfism / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D005799:Genes, Dominant; D005804:Genes, Lethal; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology; D009469:Neuromuscular Junction / Q000196:embryology / Q000502:physiology* / Q000648:ultrastructure; D009928:Organ Specificity; D010243:Paralysis / Q000151:congenital / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D019076:Transgenes
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C498595:NBEA protein, human; C403265:Nbea protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger