Department of Cell Biology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.
Semin Cell Dev Biol. 2011 Jul;22(5):499-505. doi: 10.1016/j.semcdb.2011.06.008. Epub 2011 Aug 6.
The trafficking mechanisms that control the density of synaptic AMPA-type glutamate receptors have received significant attention because of their importance for regulating excitatory synaptic transmission and synaptic plasticity in the hippocampus. AMPA receptors are synthesized in the neuronal cell body and reach their postsynaptic targets after a complex journey involving multiple transport steps along different cytoskeleton structures and through various stages of the endocytic pathway. Dendritic spines are important sites for AMPA receptor trafficking and contain the basic components of endosomal recycling. On induction of synaptic plasticity, internalized AMPA receptors undergo endosomal sorting and cycle through early endosomes and recycling endosomes back to the plasma membrane (model for long-term potentiation) or target for degradation to the lysosomes (model for long-term depression). Exciting new studies now provide insight in actin-mediated processes that controls endosomal tubule formation and receptor sorting. This review describes the path of AMPA receptor internalization up to sites of recycling and summarizes recent studies on actin-mediated endosomal receptor sorting.
控制突触 AMPA 型谷氨酸受体密度的贩运机制因其对调节海马体兴奋性突触传递和突触可塑性的重要性而受到广泛关注。AMPA 受体在神经元胞体中合成,然后通过多个运输步骤,沿着不同的细胞骨架结构进行,并通过内吞途径的各个阶段,到达其突触后靶标。树突棘是 AMPA 受体贩运的重要部位,包含内体循环的基本成分。在诱导突触可塑性时,内吞的 AMPA 受体经历内体分拣,并通过早期内体和循环内体返回质膜(长时程增强模型)或靶向溶酶体进行降解(长时程抑制模型)。令人兴奋的新研究现在提供了关于控制内体小管形成和受体分拣的肌动蛋白介导过程的深入了解。这篇综述描述了 AMPA 受体内化到循环部位的途径,并总结了最近关于肌动蛋白介导的内体受体分拣的研究。