RRC ID 46547
著者 Zhang D, Isack NR, Glodowski DR, Liu J, Chen CC, Xu XZ, Grant BD, Rongo C.
タイトル RAB-6.2 and the retromer regulate glutamate receptor recycling through a retrograde pathway.
ジャーナル J Cell Biol
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.
巻・号 196(1)
ページ 85-101
公開日 2012-1-9
DOI 10.1083/jcb.201104141
PII jcb.201104141
PMID 22213799
PMC PMC3255976
MeSH 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*
IF 8.811
引用数 31
WOS 分野 CELL BIOLOGY
リソース情報
線虫 tm847