Lee Sang Hyoung, Simonetta Alyson, Sheng Morgan
The Picower Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge 02139, USA.
Neuron. 2004 Jul 22;43(2):221-36. doi: 10.1016/j.neuron.2004.06.015.
Removal of synaptic AMPA receptors is important for synaptic depression. Here, we characterize the roles of individual subunits in the inducible redistribution of AMPA receptors from the cell surface to intracellular compartments in cultured hippocampal neurons. The intracellular accumulation of GluR2 and GluR3 but not GluR1 is enhanced by AMPA, NMDA, or synaptic activity. After AMPA-induced internalization, homomeric GluR2 enters the recycling pathway, but following NMDA, GluR2 is diverted to late endosomes/lysosomes. In contrast, GluR1 remains in the recycling pathway, and GluR3 is targeted to lysosomes regardless of NMDA receptor activation. Interaction with NSF plays a role in regulated lysosomal targeting of GluR2. GluR1/GluR2 heteromeric receptors behave like GluR2 homomers, and endogenous AMPA receptors show differential activity-dependent sorting similar to homomeric GluR2. Thus, GluR2 is a key subunit that controls recycling and degradation of AMPA receptors after internalization.
突触AMPA受体的移除对于突触抑制很重要。在此，我们阐述了各个亚基在培养的海马神经元中AMPA受体从细胞表面向细胞内区室的诱导性重新分布中的作用。AMPA、NMDA或突触活动可增强GluR2和GluR3而非GluR1在细胞内的积累。AMPA诱导内化后，同聚体GluR2进入再循环途径，但在NMDA作用后，GluR2被转移至晚期内体/溶酶体。相比之下，GluR1保留在再循环途径中，且无论NMDA受体是否激活，GluR3都靶向溶酶体。与NSF的相互作用在GluR2的调节性溶酶体靶向中发挥作用。GluR1/GluR2异聚体受体的行为类似于GluR2同聚体，内源性AMPA受体表现出与同聚体GluR2相似的差异性活性依赖性分选。因此，GluR2是控制内化后AMPA受体再循环和降解的关键亚基。
