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MARCKS regulates membrane targeting of Rab10 vesicles to promote axon development
Xiao-Hui Xu1, Cai-Yun Deng2, Yang Liu2
11] 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.
Cell Research
|March 26, 2014
Summary
Myristoylated alanine-rich C-kinase substrate (MARCKS) is crucial for axon development. It guides Rab10-positive vesicles to the membrane, ensuring proper axon growth and receptor insertion.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Axon development relies on intracellular membrane addition via plasmalemmal precursor vesicles (PPVs) mediated by Rab10.
- The precise molecular mechanisms governing PPV trafficking and membrane fusion remain largely unknown.
Purpose of the Study:
- To elucidate the molecular mechanisms of Rab10-positive PPV trafficking during axon development.
- To investigate the role of myristoylated alanine-rich C-kinase substrate (MARCKS) in this process.
Main Methods:
- Utilized genetic silencing of MARCKS in cortical neurons.
- Disrupted the interaction between MARCKS and Rab10.
- Observed effects on axon growth, vesicle docking and fusion, and membrane insertion of receptors.
Main Results:
- MARCKS mediates the membrane targeting of Rab10-positive PPVs.
- The binding affinity between Rab10 and MARCKS is regulated by the phosphorylation status of MARCKS.
- Genetic silencing of MARCKS or disruption of its interaction with Rab10 inhibited axon growth and impaired PPV fusion with the plasma membrane.
Conclusions:
- MARCKS plays a critical, novel role in targeting PPVs to the plasma membrane during axon development.
- This MARCKS-mediated targeting is essential for the insertion of axonal receptors and overall axon growth.
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