POSH localizes activated Rac1 to control the formation of cytoplasmic dilation of the leading process and neuronal migration
Saturday, Oct 13, 2012, 1:00 PM - 2:00 PM
, T. YANG;
Inst. of Genet. and Developmental Biol., Beijing, China
Radial migration of neurons plays a pivotal role in neocortical lamination. The formation of proximal cytoplasmic dilation in the leading process (PCDLP) of migratory neocortical neurons is crucial for somal translocation and neuronal migration, processes which require the elaborate coordination of F-actin dynamics, centrosomal movement and nucleokinesis. However, the underlying molecular mechanisms remain poorly understood.
We have shown previously that POSH (plenty of SH3s) interacts with JIPs to serve as scaffold proteins for a JNK pathway protein complex. Many components of this complex are indispensable for radial migration in the developing brain. An intriguing question remains to be answered is whether and how POSH might regulate radial migration in the developing brain.
Here we show that, the Rac1-interacting scaffold protein POSH, is essential for neuronal migration in vivo. We demonstrate that POSH is concentrated in the PCDLP and knockdown of POSH impairs PCDLP formation, centrosome translocation and nucleokinesis. Furthermore, POSH co-localizes with F-actin and the activated form of Rac1. Interestingly, knockdown of POSH impairs F-actin assembly and delocalizes activated Rac1. Interference of Rac1 activity also disrupts F-actin assembly, PCDLP formation and perturbs neuronal migration. Thus, we have uncovered a novel mechanism by which POSH regulates the localization of activated Rac1 and F-actin assembly to control PCDLP formation and subsequent somal translocation of migratory neurons.
Related publications (* Corresponding author)
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2. Ren J.....and Xu Z* (2010) J Biol Chem.
3. Xu Z.*⋯ and Greene L. (2006) J Biol Chem.
4. Xu Z.*, Kukekov, N., and Greene L (2005) Mol Cell Biol.
5. Xu Z., Kukekov N., and Greene LA (2003). EMBO J
MOST (China) “973” program (2007CB947202)
NSF (China) (30725007/30670663)
[Authors]. [Abstract Title]. Program No. XXX.XX. 2012 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2012. Online.
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