title: Dab2IP GTPase activating protein regulates dendrite development and synapse number in cerebellum.
abstract: DOC-2/DAB-2 interacting protein (Dab2IP) is a GTPase activating protein that binds to Disabled-1, a cytosolic adapter protein involved in Reelin signaling and brain development. Dab2IP regulates PI3K-AKT signaling and is associated with metastatic prostate cancer, abdominal aortic aneurysms and coronary heart disease. To date, the physiological function of Dab2IP in the nervous system, where it is highly expressed, is relatively unknown. In this study, we generated a mouse model with a targeted disruption of Dab2IP using a retrovirus gene trap strategy. Unlike reeler mice, Dab2IP knock-down mice did not exhibit severe ataxia or cerebellar hypoplasia. However, Dab2IP deficiency produced a number of cerebellar abnormalities such as a delay in the development of Purkinje cell (PC) dendrites, a decrease in the parallel fiber synaptic marker VGluT1, and an increase in the climbing fiber synaptic marker VGluT2. These findings demonstrate for the first time that Dab2IP plays an important role in dendrite development and regulates the number of synapses in the cerebellum.
authors: Department of Biological Sciences, University of Memphis, Memphis, Tennessee, United States of America.
authors: Shuhong
authors: S
authors: Qiao
authors: Sun-Hong
authors: SH
authors: Kim
authors: Detlef
authors: D
authors: Heck
authors: Daniel
authors: D
authors: Goldowitz
authors: Mark S
authors: MS
authors: LeDoux
authors: Ramin
authors: R
authors: Homayouni
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology* / Q000201:enzymology*; D003712:Dendrites / Q000201:enzymology*; D005260:Female; D055785:Gene Knockdown Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D019599:Mossy Fibers, Hippocampal / Q000201:enzymology; D055495:Neurogenesis; D021381:Protein Transport; D011689:Purkinje Cells / Q000166:cytology / Q000201:enzymology; D000091042:Reelin Protein; D015203:Reproducibility of Results; D013569:Synapses / Q000201:enzymology*; D020703:ras GTPase-Activating Proteins / Q000172:deficiency / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C561450:Dab2ip protein, mouse; D000091042:Reelin Protein; D020703:ras GTPase-Activating Proteins; C000717128:Reln protein, mouse