Volume 24, No 5, May 2014
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 24 Issue 5, May 2014: 576-594
ORIGINAL ARTICLES
MARCKS regulates membrane targeting of Rab10 vesicles to promote axon development
Xiao-Hui Xu1,2,*, Cai-Yun Deng1,*, Yang Liu1, Miao He1, Jian Peng1,3, Tong Wang1, Lei Yuan1, Zhi-Sheng Zheng1, Perry J Blackshear4 and Zhen-Ge Luo1
1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2School of Life Sciences, Shanghai University, Shanghai 200444, China
3School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China
4Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Correspondence: Zhen-Ge Luo,(zgluo@ion.ac.cn)
Axon development requires membrane addition from the intracellular supply, which has been shown to be mediated by Rab10-positive plasmalemmal precursor vesicles (PPVs). However, the molecular mechanisms underlying the membrane trafficking processes of PPVs remain unclear. Here, we show that myristoylated alanine-rich C-kinase substrate (MARCKS) mediates membrane targeting of Rab10-positive PPVs, and this regulation is critical for axon development. We found that the GTP-locked active form of Rab10 binds to membrane-associated MARCKS, whose affinity depends on the phosphorylation status of the MARCKS effector domain. Either genetic silencing of MARCKS or disruption of its interaction with Rab10 inhibited axon growth of cortical neurons, impaired docking and fusion of Rab10 vesicles with the plasma membrane, and consequently caused a loss of membrane insertion of axonal receptors responsive to extracellular axon growth factors. Thus, this study has identified a novel function of MARCKS in mediating membrane targeting of PPVs during axon development.
10.1038/cr.2014.33
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