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J Cell Biol. 2012 Jan 9;196(1):85-101. doi: 10.1083/jcb.201104141. Epub 2012 Jan 2.

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

Author information

1
The Waksman Institute, Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.

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.

PMID:
22213799
PMCID:
PMC3255976
DOI:
10.1083/jcb.201104141
[Indexed for MEDLINE]
Free PMC Article

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