Dab2IP GTPase Activating Protein Regulates Dendrite Development and Synapse Number in Cerebellum

• Published in: PloS one Vol. 8; no. 1; p. e53635
• Main Authors: Qiao, Shuhong, Kim, Sun-Hong, Heck, Detlef, Goldowitz, Daniel, LeDoux, Mark S., Homayouni, Ramin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.01.2013; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Abnormalities; Adapter proteins; Adapters; AKT protein; Analysis; Aneurysm; Animals; Aorta; Apoptosis; Ataxia; Biology; Biomarkers - metabolism; Brain; Cancer metastasis; Cardiovascular disease; Cardiovascular diseases; Cerebellum; Cerebellum - cytology; Cerebellum - enzymology; Climbing; Coronary artery disease; Coronary heart disease; Dendrites; Dendrites - enzymology; Dietary fiber; Disabled-1 protein; Female; Gene Knockdown Techniques; Guanosine triphosphatases; Heart diseases; Hypoplasia; Kinases; Metastases; Mice; Mice, Inbred C57BL; Mossy Fibers, Hippocampal - enzymology; Nervous system; Neurobiology; Neurogenesis; Neurology; Neurons; Neurosciences; Physiological aspects; Prostate cancer; Protein binding; Protein Transport; Purkinje Cells - cytology; Purkinje Cells - enzymology; ras GTPase-Activating Proteins - deficiency; ras GTPase-Activating Proteins - metabolism; Reelin Protein; Regulation; Reproducibility of Results; Science; Signaling; Synapses; Synapses - enzymology; United States > US; Tennessee
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053635

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.