Journal article
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
Journal of neurogenetics, Vol.29(2-3), pp.135-143
07/03/2015
DOI: 10.3109/01677063.2015.1064916
PMCID: PMC4747641
PMID: 26100104
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.
Details
- Title: Subtitle
- 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
- Creators
- Alexandria Wise - Department of Biology, City College of New YorkLuis Tenezaca - Department of Biology, City College of New YorkRobert W Fernandez - Department of Molecular Biophysics and Biochemistry, Yale UniversityEmma Schatoff - Department of Biology, City College of New YorkJulian Flores - Department of Biology, City College of New YorkAtsushi Ueda - Department of Biology, University of IowaXiaotian Zhong - Department of Biology, University of IowaChun-Fang Wu - Department of Biology, University of IowaAnne F Simon - Department of Biology,Western UniversityTadmiri Venkatesh - Department of Biology, City College of New York
- Resource Type
- Journal article
- Publication Details
- Journal of neurogenetics, Vol.29(2-3), pp.135-143
- DOI
- 10.3109/01677063.2015.1064916
- PMID
- 26100104
- PMCID
- PMC4747641
- NLM abbreviation
- J Neurogenet
- ISSN
- 0167-7063
- eISSN
- 1563-5260
- Publisher
- Informa UK Limited
- Language
- English
- Date published
- 07/03/2015
- Academic Unit
- Iowa Neuroscience Institute; Biology
- Record Identifier
- 9984070405202771
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