title: TC10β/CDC42 GTPase activating protein is required for the growth of cortical neuron dendrites.
abstract: Neuronal morphogenesis plays an important role in neuronal development. TC10β/CDC42 GTPase-activating protein (TCGAP) is known to be a brain-enriched multiple domain protein, but its role in neuronal development process remains poorly understood. In the present study, we showed that TCGAP positively regulated dendritic outgrowth and spine formation in developing cortical neurons. Knocking down TCGAP by RNA interference led to a decrease in the overall length of dendrite arbors and the number of dendrite branches both in vitro and in vivo. Overexpressing TCGAP in cultured cortical neurons increased dendritic outgrowth and branching. Moreover, overexpressing TCGAP lead to an increase of spine density while knocking-down TCGAP decreased spine density in vivo. The defect by downregulating TCGAP could be rescued by expressing a knock-down resistant form of TCGAP both in vivo and in vitro. In contrast, neither downregulating nor overexpressing TCGAP had any effect on axonal morphogenesis in primary cortical neuron cultures. Together, our findings suggest that TCGAP regulates neuronal morphogenesis in developing cortical neurons at both early and late stage.
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: P-C
authors.initials: PC
authors.lastname: Shen
authors.forename: D-F
authors.initials: DF
authors.lastname: Xu
authors.forename: J-W
authors.initials: JW
authors.lastname: Liu
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Lin
authors.forename: H-T
authors.initials: HT
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure*; D018274:Electroporation; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D020690:GTPase-Activating Proteins