RAB-6.2 and the Retromer Regulate Glutamate Receptor Recycling Through a Retrograde Pathway

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / analysis
  • Caenorhabditis elegans Proteins / metabolism*
  • Caenorhabditis elegans Proteins / physiology
  • Endocytosis
  • Endosomes / metabolism
  • Golgi Apparatus / metabolism
  • Membrane Proteins / analysis
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology
  • Protein Transport
  • Receptors, AMPA / metabolism*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism
  • rab GTP-Binding Proteins / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Receptors, AMPA
  • glr-1 protein, C elegans
  • lin-10 protein, C elegans
  • RAB-6.2 protein, C elegans
  • rab GTP-Binding Proteins