RGD Reference Report - p250GAP is a novel player in the Cdh1-APC/Smurf1 pathway of axon growth regulation. - Rat Genome Database

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p250GAP is a novel player in the Cdh1-APC/Smurf1 pathway of axon growth regulation.

Authors: Kannan, Madhuvanthi  Lee, Shih-Ju  Schwedhelm-Domeyer, Nicola  Nakazawa, Takanobu  Stegmüller, Judith 
Citation: Kannan M, etal., PLoS One. 2012;7(11):e50735. doi: 10.1371/journal.pone.0050735. Epub 2012 Nov 30.
RGD ID: 151665335
Pubmed: (View Article at PubMed) PMID:23226367
DOI: Full-text: DOI:10.1371/journal.pone.0050735

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.

Gene Ontology Annotations    

Biological Process

Cellular Component
cytoplasm  (IDA)

Objects Annotated

Genes (Rattus norvegicus)
Arhgap32  (Rho GTPase activating protein 32)
Cdh1  (cadherin 1)
Smurf1  (SMAD specific E3 ubiquitin protein ligase 1)

Additional Information