RAB-6.2 and the retromer regulate glutamate receptor recycling through a retrograde pathway.
RAB-6.2 and the retromer regulate glutamate receptor recycling through a retrograde pathway.
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DOI：
10.1083/jcb.201104141
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发表时间：
2012-01-09
期刊：
影响因子：
--
通讯作者：
Rongo C
中科院分区：
文献类型：
--
作者：
Zhang D;Isack NR;Glodowski DR;Liu J;Chen CC;Xu XZ;Grant BD;Rongo C
RAB-6.2、其效应子LIN-10和逆转录复合物通过沿逆行转运途径再循环突触后谷氨酸受体沿着来维持突触强度。AMPA型谷氨酸受体（AMPAR）的调节膜运输是突触可塑性的关键机制，但AMPAR使用的途径还没有得到很好的理解。在本文中，我们表明，在秀丽隐杆线虫的AMPAR亚基GLR-1利用逆行转运途径来调节AMPAR突触丰度。rab-6.2、retromer基因vps-35和snx-1以及rme-8的突变体未能回收GLR-1受体，导致GLR-1周转和行为缺陷，表明GLR-1功能减弱。相反，组成型活性RAB-6.2的表达驱动GLR-1从树突逆行转运回细胞体高尔基体。我们还发现，激活的RAB-6.2绑定和共定位与PDZ/磷酸酪氨酸结合域蛋白LIN-10。RAB-6.2招募LIN-10。此外，RAB-6.2对GLR-1转运的调节需要LIN-10活性。我们的研究结果表明，RAB-6.2，其效应LIN-10，和retromer复合物在维持突触强度通过回收AMPAR沿着逆行运输途径的新作用。
RAB-6.2, its effector LIN-10, and the retromer complex maintain synaptic strength by recycling postsynaptic glutamate receptors along the retrograde transport 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.
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影响因子：
15.9
作者：
Henley, Jeremy M.;Barker, Ellen A.;Glebov, Oleg O.
通讯作者：
Glebov, Oleg O.
影响因子：
16.2
作者：
Brockie PJ;Maricq AV
通讯作者：
Maricq AV
影响因子：
64.8
作者：
Jaillais, Yvon;Fobis-Loisy, Isabelle;Gaude, Thierry
通讯作者：
Gaude, Thierry
影响因子：
3.3
作者：
Chun, Denise K.;McEwen, Jason M.;Kaplan, Joshua M.
通讯作者：
Kaplan, Joshua M.
DOI：
10.1073/pnas.0503689102
发表时间：
2005-09-20
影响因子：
11.1
作者：
Andersen, OM;Reiche, J;Willnow, TE
通讯作者：
Willnow, TE