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

Shuhong Qiao, Sun Hong Kim, Detlef Heck, Daniel Goldowitz, Mark Ledoux, Ramin Homayouni

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere53635
JournalPLoS One
Volume8
Issue number1
DOIs
StatePublished - Jan 9 2013

Fingerprint

GTPase-activating proteins
GTPase-Activating Proteins
dendrites
cerebellum
synapse
Dendrites
Synapses
Cerebellum
Proteins
proteins
Retroviridae
Neurologic Mutant Mice
aneurysm
Protein Deficiency
protein deficiencies
Purkinje Cells
mice
Abdominal Aortic Aneurysm
phosphatidylinositol 3-kinase
prostatic neoplasms

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Dab2IP GTPase Activating Protein Regulates Dendrite Development and Synapse Number in Cerebellum. / Qiao, Shuhong; Kim, Sun Hong; Heck, Detlef; Goldowitz, Daniel; Ledoux, Mark; Homayouni, Ramin.

In: PLoS One, Vol. 8, No. 1, e53635, 09.01.2013.

Research output: Contribution to journalArticle

Qiao, Shuhong ; Kim, Sun Hong ; Heck, Detlef ; Goldowitz, Daniel ; Ledoux, Mark ; Homayouni, Ramin. / Dab2IP GTPase Activating Protein Regulates Dendrite Development and Synapse Number in Cerebellum. In: PLoS One. 2013 ; Vol. 8, No. 1.
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