title: MARCKS regulates membrane targeting of Rab10 vesicles to promote axon development.
abstract: 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.
authors.affiliation: 1] Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2] School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Xu
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Deng
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.affiliation: 1] Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2] School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Peng
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Zheng
authors.affiliation: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Perry J
authors.initials: PJ
authors.lastname: Blackshear
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhen-Ge
authors.initials: ZG
authors.lastname: Luo
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism*; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; C000619712:Marcks protein, rat; D008565:Membrane Proteins; C082378:Rab10 protein, rat; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D020691:rab GTP-Binding Proteins