RAB-6.2 and the retromer regulate glutamate receptor recycling through a retrograde pathway.

Donglei Zhang, Nora R Isack, Doreen R Glodowski, Jie Liu, Carlos Chih-Hsiung Chen, X Z Shawn Xu, Barth D Grant, Christopher Rongo

The Journal of cell biology 2012 Jan 9

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Regulated membrane trafficking of AMPA-type glutamate receptors (AMPARs) is a key mechanism underlying synaptic plasticity, yet the pathways used by AMPARs are not well understood. In this paper, we show that the AMPAR subunit GLR-1 in Caenorhabditis elegans utilizes the retrograde transport pathway to regulate AMPAR synaptic abundance. Mutants for rab-6.2, the retromer genes vps-35 and snx-1, and rme-8 failed to recycle GLR-1 receptors, resulting in GLR-1 turnover and behavioral defects indicative of diminished GLR-1 function. In contrast, expression of constitutively active RAB-6.2 drove the retrograde transport of GLR-1 from dendrites back to cell body Golgi. We also find that activated RAB-6.2 bound to and colocalized with the PDZ/phosphotyrosine binding domain protein LIN-10. RAB-6.2 recruited LIN-10. Moreover, the regulation of GLR-1 transport by RAB-6.2 required LIN-10 activity. Our results demonstrate a novel role for RAB-6.2, its effector LIN-10, and the retromer complex in maintaining synaptic strength by recycling AMPARs along the retrograde transport pathway.

Citation

Donglei Zhang, Nora R Isack, Doreen R Glodowski, Jie Liu, Carlos Chih-Hsiung Chen, X Z Shawn Xu, Barth D Grant, Christopher Rongo. RAB-6.2 and the retromer regulate glutamate receptor recycling through a retrograde pathway. The Journal of cell biology. 2012 Jan 9;196(1):85-101