RAB-6.2 and the retromer regulate glutamate receptor recycling through a retrograde pathway.
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.
The Waksman Institute, Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Donglei
D
Zhang
Nora R
NR
Isack
Doreen R
DR
Glodowski
Jie
J
Liu
Carlos Chih-Hsiung
CC
Chen
X Z Shawn
XZ
Xu
Barth D
BD
Grant
Christopher
C
Rongo
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; C096470:glr-1 protein, C elegans; C064105:lin-10 protein, C elegans; C571036:RAB-6.2 protein, C elegans; D020691:rab GTP-Binding Proteins