RAB-10 regulates glutamate receptor recycling in a cholesterol-dependent endocytosis pathway

Mol Biol Cell. 2007 Nov;18(11):4387-96. doi: 10.1091/mbc.e07-05-0486. Epub 2007 Aug 29.


Regulated endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) is critical for synaptic plasticity. However, the specific combination of clathrin-dependent and -independent mechanisms that mediate AMPAR trafficking in vivo have not been fully characterized. Here, we examine the trafficking of the AMPAR subunit GLR-1 in Caenorhabditis elegans. GLR-1 is localized on synaptic membranes, where it regulates reversals of locomotion in a simple behavioral circuit. Animals lacking RAB-10, a small GTPase required for endocytic recycling of intestinal cargo, are similar in phenotype to animals lacking LIN-10, a postsynaptic density 95/disc-large/zona occludens-domain containing protein: GLR-1 accumulates in large accretions and animals display a decreased frequency of reversals. Mutations in unc-11 (AP180) or itsn-1 (Intersectin 1), which reduce clathrin-dependent endocytosis, suppress the lin-10 but not rab-10 mutant phenotype, suggesting that LIN-10 functions after clathrin-mediated endocytosis. By contrast, cholesterol depletion, which impairs lipid raft formation and clathrin-independent endocytosis, suppresses the rab-10 but not the lin-10 phenotype, suggesting that RAB-10 functions after clathrin-independent endocytosis. Animals lacking both genes display additive GLR-1 trafficking defects. We propose that RAB-10 and LIN-10 recycle AMPARs from intracellular endosomal compartments to synapses along distinct pathways, each with distinct sensitivities to cholesterol and the clathrin-mediated endocytosis machinery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cholesterol / pharmacology*
  • Endocytosis / drug effects*
  • Membrane Proteins / metabolism
  • Mutation / genetics
  • Nerve Tissue Proteins / metabolism
  • Phenotype
  • Receptors, AMPA / metabolism
  • Receptors, Glutamate / metabolism*
  • Signal Transduction
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*


  • Adaptor Proteins, Vesicular Transport
  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, AMPA
  • Receptors, Glutamate
  • glr-1 protein, C elegans
  • lin-10 protein, C elegans
  • unc-11 protein, C elegans
  • Cholesterol
  • RAB-10 protein, C elegans
  • rab GTP-Binding Proteins