title: Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, and impaired adult social behavior and activity patterns.
abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions, and hyperactivity. ASD exhibits a strong genetic component with underlying multigene interactions. Candidate gene studies have shown that the neurobeachin (NBEA) gene is disrupted in human patients with idiopathic autism ( Castermans et al., 2003 ). The NBEA gene spans the common fragile site FRA 13A and encodes a signal scaffold protein ( Savelyeva et al., 2006 ). In mice, NBEA has been shown to be involved in the trafficking and function of a specific subset of synaptic vesicles. ( Medrihan et al., 2009 ; Savelyeva et al., 2006 ). Rugose (rg) is the Drosophila homolog of the mammalian and human NBEA. Our previous genetic and molecular analyses have shown that rg encodes an A kinase anchor protein (DAKAP 550), which interacts with components of the epidermal growth factor receptor or EGFR and Notch-mediated signaling pathways, facilitating cross talk between these and other pathways ( Shamloula et al., 2002 ). We now present functional data from studies on the larval neuromuscular junction that reveal abnormal synaptic architecture and physiology. In addition, adult rg loss-of-function mutants exhibit defective social interactions, impaired habituation, aberrant locomotion, and hyperactivity. These results demonstrate that Drosophila NBEA (rg) mutants exhibit phenotypic characteristics reminiscent of human ASD and thus could serve as a genetic model for studying ASDs.
authors.affiliation: a Department of Biology , City College of New York , NY , USA.
authors.forename: Alexandria
authors.initials: A
authors.lastname: Wise
authors.affiliation: a Department of Biology , City College of New York , NY , USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Tenezaca
authors.affiliation: b Department of Molecular Biophysics and Biochemistry , Yale University , New Haven, Connecticut , USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Fernandez
authors.affiliation: a Department of Biology , City College of New York , NY , USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Schatoff
authors.affiliation: a Department of Biology , City College of New York , NY , USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Flores
authors.affiliation: c Department of Biology , University of Iowa , Iowa City , IA , USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ueda
authors.affiliation: c Department of Biology , University of Iowa , Iowa City , IA , USA.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Zhong
authors.affiliation: c Department of Biology , University of Iowa , Iowa City , IA , USA.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Wu
authors.affiliation: d Department of Biology,Western University , Ontario , Canada.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Simon
authors.affiliation: a Department of Biology , City College of New York , NY , USA.
authors.forename: Tadmiri
authors.initials: T
authors.lastname: Venkatesh
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster; D008124:Locomotion / Q000235:genetics*; D009043:Motor Activity / Q000235:genetics*; D009154:Mutation; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012919:Social Behavior; D013569:Synapses / Q000235:genetics* / Q000378:metabolism
chemical_list: D054758:A Kinase Anchor Proteins; D029721:Drosophila Proteins; C108769:rg protein, Drosophila
keywords: Autism spectrum disorder; Drosophila; neurobeachin; neuromuscular junction; rugose; synaptic development