title: p250GAP is a novel player in the Cdh1-APC/Smurf1 pathway of axon growth regulation.
abstract: Axon growth is an essential process during brain development. The E3 ubiquitin ligase Cdh1-APC has emerged as a critical regulator of intrinsic axon growth control. Here, we identified the RhoGAP p250GAP as a novel interactor of the E3 ubiquitin ligase Cdh1-APC and found that p250GAP promotes axon growth downstream of Cdh1-APC. We also report that p250GAP undergoes non-proteolytic ubiquitination and associates with the Cdh1 substrate Smurf1 to synergistically regulate axon growth. Finally, we found that in vivo knockdown of p250GAP in the developing cerebellar cortex results in impaired migration and axonal growth. Taken together, our data indicate that Cdh1-APC together with the RhoA regulators p250GAP and Smurf1 controls axon growth in the mammalian brain.
authors.affiliation: Cellullar and Molecular Neurobiology, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Madhuvanthi
authors.initials: M
authors.lastname: Kannan
authors.forename: Shih-Ju
authors.initials: SJ
authors.lastname: Lee
authors.forename: Nicola
authors.initials: N
authors.lastname: Schwedhelm-Domeyer
authors.forename: Takanobu
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Judith
authors.initials: J
authors.lastname: Stegmüller
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD; D001369:Axons / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D051381:Rats; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C555337:APC protein, human; C470196:ARHGAP32 protein, human; D025601:Adenomatous Polyposis Coli Protein; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D020690:GTPase-Activating Proteins; C085379:rho GTPase-activating protein; C498342:SMURF1 protein, human; D044767:Ubiquitin-Protein Ligases