Gulia Ravinder, Sharma Rohan, Bhattacharyya Samarjit
From the Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Knowledge City, Sector 81, SAS Nagar, PO 140306, Punjab, India.
From the Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Knowledge City, Sector 81, SAS Nagar, PO 140306, Punjab, India
J Biol Chem. 2017 Jan 27;292(4):1426-1437. doi: 10.1074/jbc.M116.752105. Epub 2016 Dec 23.
Group I metabotropic glutamate receptors (mGluRs) play important roles in various neuronal processes and elicit changes in synaptic efficacy through AMPA receptor (AMPAR) endocytosis. Trafficking of mGluRs plays an important role in controlling the precise localization of these receptors at specific region of the cell; it also regulates the activity of these receptors. Despite this obvious significance, we know very little about the cellular mechanisms that control the trafficking of group I mGluRs. We show here that ligand-mediated internalization of group I mGluRs is ubiquitination-dependent. A lysine residue (Lys) at the C-terminal tail of mGluR1 (a member of the group I mGluR family) plays crucial role in this process. Our data suggest that Lys-linked polyubiquitination is involved in the ligand-mediated endocytosis of mGluR1. We also show here that the mGluR1 internalization is dependent on a specific E3 ubiquitin ligase, Siah-1A. Furthermore, acute knockdown of Siah-1A enhances the mGluR-mediated AMPAR endocytosis. These studies reveal a novel function of ubiquitination in the regulation of group I mGluRs, as well as its role in mGluR-dependent AMPAR endocytosis.
I 型代谢型谷氨酸受体（mGluRs）在各种神经元过程中发挥重要作用，并通过AMPA受体（AMPAR）内吞作用引起突触效能的变化。mGluRs的转运在控制这些受体在细胞特定区域的精确定位中起重要作用；它还调节这些受体的活性。尽管具有明显的重要性，但我们对控制I型mGluRs转运的细胞机制知之甚少。我们在此表明，I型mGluRs的配体介导的内化是泛素化依赖性的。mGluR1（I型mGluR家族的成员）C末端尾巴上的一个赖氨酸残基（Lys）在此过程中起关键作用。我们的数据表明，赖氨酸连接的多聚泛素化参与了mGluR1的配体介导的内吞作用。我们在此还表明，mGluR1的内化依赖于一种特定的E3泛素连接酶Siah-1A。此外，急性敲低Siah-1A可增强mGluR介导的AMPAR内吞作用。这些研究揭示了泛素化在调节I型mGluRs中的新功能，以及其在mGluR依赖性AMPAR内吞作用中的作用。
