Abstract
The Par polarity complex consisting of the evolutionarily conserved proteins mPar3, mPar6, and aPKC regulates cell polarity in many cell types including neurons. Here we show that mPar3 is required for the establishment of neuronal polarity and links the Smurf2 to Kinesin-2. The HECT domain E3 ubiquitin ligase Smurf2 ensures that neurons extend only a single axon by initiating the degradation of inactive Rap1B through the ubiquitin/proteasome system. Its interaction with mPar3 is required to localize Smurf2 to growth cones and restrict Rap1B to the axon. Interfering with the binding of mPar3 to Kinesin-2 or Smurf2 to mPar3 and knockdown of mPar3 by RNAi disrupt the establishment of neuronal polarity through the failure to restrict Rap1B to a single neurite.
Highlights
During the differentiation of hippocampal neurons, unpolarized cells initially form several equivalent neurites, all of which have the potential to become an axon [1]
Smad ubiquitination regulatory factor-1 (Smurf1) and Smurf2 are originally identified as HECT domain E3 ubiquitin ligases that interact with Smad proteins [17, 18]
We show that Smurf2 interacts with mPar3 and that this interaction is required for linking Smurf2 to KIF3A and the localization of Smurf2 to growth cones. mPar3-mediated localization is essential for the establishment of neuronal polarity by initiating the degradation of Rap1B and restricting it to a single neurite
Summary
During the differentiation of hippocampal neurons, unpolarized cells initially form several equivalent neurites, all of which have the potential to become an axon (stage 2) [1]. Its interaction with mPar3 is required to localize Smurf2 to growth cones and restrict Rap1B to the axon. Interfering with the binding of mPar3 to Kinesin-2 or Smurf2 to mPar3 and knockdown of mPar3 by RNAi disrupt the establishment of neuronal polarity through the failure to restrict Rap1B to a single neurite.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
