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

Research output: Contribution to journalArticleResearchpeer-review

40 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number22213799
Pages (from-to)85-101
Number of pages17
JournalJournal of Cell Biology
Volume196
Issue number1
DOIs
Publication statusPublished - 2012
Externally publishedYes

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