Fukata Masaki, Fukata Yuko
Division of Membrane Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2008 Jun;28(3):131-4.
Finely tuned synaptic transmission in the brain provides the molecular basis for learning and memory. The misregulation of synaptic transmission is involved in the pathogenesis of various neurological disorders like epilepsy. AMPA-typed glutamate receptors (AMPARs) mediate the most prominent form of excitatory neurotransmission in the brain. Dynamic regulation of AMPARs is thought to be a primary mechanism for controlling synaptic strength. We have analyzed the molecular mechanism for AMPAR-trafficking and function by focusing on PSD-95, a major postsynaptic scaffolding protein. Here, we review the novel regulatory mechanisms of AMPARs by 1) the PSD-95 palmitoylating enzyme, which determines the position of PSD-95 at postsynapses, and 2) the epilepsy related ligand/receptor, LGI1/ADAM22, identified as the PSD-95-interacting protein.
大脑中精确调节的突触传递为学习和记忆提供了分子基础。突触传递的失调与癫痫等各种神经系统疾病的发病机制有关。AMPA型谷氨酸受体（AMPARs）介导大脑中最主要的兴奋性神经传递形式。AMPA受体的动态调节被认为是控制突触强度的主要机制。我们通过聚焦于主要的突触后支架蛋白PSD-95，分析了AMPAR转运和功能的分子机制。在此，我们通过以下两方面综述AMPARs的新型调节机制：1）PSD-95棕榈酰化酶，其决定了PSD-95在突触后的位置；2）癫痫相关配体/受体LGI1/ADAM22，其被鉴定为与PSD-95相互作用的蛋白。
