Greger Ingo H, Khatri Latika, Ziff Edward B
Howard Hughes Medical Institute, Department of Biochemistry, NYU School of Medicine, New York 10016, USA.
Neuron. 2002 May 30;34(5):759-72. doi: 10.1016/s0896-6273(02)00693-1.
AMPA-receptor (AMPAR) transport to synapses plays a critical role in the modulation of synaptic strength. We show that the functionally critical GluR2 subunit stably resides in an intracellular pool in the endoplasmic reticulum (ER). GluR2 in this pool is extensively complexed with GluR3 but not with GluR1, which is mainly confined to the cell surface. Mutagenesis revealed that elements in the C terminus including the PDZ motif are required for GluR2 forward-transport from the ER. Surprisingly, ER retention of GluR2 is controlled by Arg607 at the Q/R-editing site. Reversion to Gln (R607Q) resulted in rapid release from the pool and elevated surface expression of GluR2 in neurons. Therefore, Arg607 is a central regulator. In addition to channel gating, it also controls ER exit and may thereby ensure the availability of GluR2 for assembly into AMPARs.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)向突触的转运在突触强度的调节中起关键作用。我们发现,功能关键的GluR2亚基稳定地存在于内质网(ER)的细胞内池中。该池中GluR2与GluR3广泛结合,但不与主要局限于细胞表面的GluR1结合。诱变显示,包括PDZ基序在内的C末端元件是GluR2从内质网正向转运所必需的。令人惊讶的是,GluR2在内质网的滞留受Q/R编辑位点的Arg607控制。突变为谷氨酰胺(R607Q)导致其迅速从池中释放,并提高了神经元中GluR2的表面表达。因此,Arg607是一个核心调节因子。除了通道门控外,它还控制内质网出口,从而可能确保GluR2可用于组装成AMPAR。