2015/06/23 by Alexandria Wise, Luis Tenezaca, Robert W. Fernandez +10
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Autism Spectrum Disorder Research #Genetics and Neurodevelopmental Disorders #Neurobiology and Insect Physiology Research
paper · doi:10.3109/01677063.2015.1064916
openalex publication_date 2015/06/23 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/29
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 Castermans, D., Wilquet, V., Parthoens, E., Huysmans, C., Steyaert, J., Swinnen, L., et al. (2003). The neurobeachin gene is disrupted by a translocation in a patient with idiopathic autism. J Med Genet, 40, 352–356.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). The NBEA gene spans the common fragile site FRA 13A and encodes a signal scaffold protein (Savelyeva et al., 2006 Savelyeva, L., Sagulenko, E., Schmitt, J. G., & Schwab, M. (2006). The neurobeachin gene spans the common fragile site FRA13A. Hum Genet, 118, 551–558. doi: 10.1007/s00439-005-0083-z[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). 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 Medrihan, L., Rohlmann, A., Fairless, R., Andrae, J., Doring, M., Missler, M., et al. (2009). Neurobeachin, a protein implicated in membrane protein traffic and autism, is required for the formation and functioning of central synapses. J Physiol, 587, 5095–5106. doi: 10.1113/jphysiol.2009.178236[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Savelyeva et al., 2006 Savelyeva, L., Sagulenko, E., Schmitt, J. G., & Schwab, M. (2006). The neurobeachin gene spans the common fragile site FRA13A. Hum Genet, 118, 551–558. doi: 10.1007/s00439-005-0083-z[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). 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 Shamloula, H. K., Mbogho, M. P., Pimentel, A. C., Chrzanowska-Lightowlers, Z. M., Hyatt, V., Okano, H., & Venkatesh, T. R. (2002). rugose (rg), a Drosophila A kinase anchor protein, is required for retinal pattern formation and interacts genetically with multiple signaling pathways. Genetics, 161, 693–710.[PubMed], [Web of Science ®] , [Google Scholar]). 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.