The E3 ligase Cdh1-anaphase promoting complex operates upstream of the E3 ligase Smurf1 in the control of axon growth
Citations Over TimeTop 13% of 2012 papers
Abstract
Axon growth is an essential event during brain development and is extremely limited due to extrinsic and intrinsic inhibition in the adult brain. The E3 ubiquitin ligase Cdh1-anaphase promoting complex (APC) has emerged as an important intrinsic suppressor of axon growth. In this study, we identify in rodents the E3 ligase Smurf1 as a novel substrate of Cdh1-APC and that Cdh1 targets Smurf1 for degradation in a destruction box-dependent manner. We find that Smurf1 acts downstream of Cdh1-APC in axon growth and that the turnover of RhoA by Smurf1 is important in this process. In addition, we demonstrate that acute knockdown of Smurf1 in vivo in the developing cerebellar cortex results in impaired axonal growth and migration. Finally, we show that a stabilized form of Smurf1 overrides the inhibition of axon growth by myelin. Taken together, we uncovered a Cdh1-APC/Smurf1/RhoA pathway that mediates axonal growth suppression in the developing mammalian brain.
Related Papers
- → Ubiquitination and Degradation of Mutant p53(2007)224 cited
- → The Ubiquitin E3 Ligase MaLUL2 Is Involved in High Temperature-Induced Green Ripening in Banana Fruit(2020)22 cited
- → Promiscuous Interactions of gp78 E3 Ligase CUE Domain with Polyubiquitin Chains(2012)33 cited
- → The poxvirus encoded ubiquitin ligase, p28, is regulated by proteasomal degradation and autoubiquitination(2014)11 cited
- → The Antibiotic Treatment Index: A Novel Tool to Improve Antibiotic Resistance Monitoring(2014)