POSH Localizes Activated Rac1 to Control the Formation of Cytoplasmic Dilation of the Leading Process and Neuronal Migration
Tao Yang,
Yiming Sun,
Feng Zhang,
Yuangang Zhu,
Lei Shi,
Huashun Li,
Zhiheng Xu
Affiliations
Tao Yang
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Yiming Sun
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Feng Zhang
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Yuangang Zhu
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Lei Shi
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
Huashun Li
West China Developmental and Stem Cell Institute, Sichuan University, West China Women’s and Children’s Hospital, Sichuan 610041, China
Zhiheng Xu
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
The formation of proximal cytoplasmic dilation in the leading process (PCDLP) of migratory neocortical neurons is crucial for somal translocation and neuronal migration, processes that require the elaborate coordination of F-actin dynamics, centrosomal movement, and nucleokinesis. However, the underlying molecular mechanisms remain poorly understood. 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 that knockdown of POSH impairs PCDLP formation, centrosome translocation, and nucleokinesis. Furthermore, POSH colocalizes with F-actin and the activated form of Rac1. Knockdown of POSH impairs F-actin assembly and delocalizes activated Rac1. Interference of Rac1 activity also disrupts F-actin assembly and PCDLP formation and perturbs neuronal migration. Thus, we have uncovered a 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.