Solomon H. Snyder Department of Neuroscience,Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and.
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane 4072, Queensland, Australia.
Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):11840-5. doi: 10.1073/pnas.1412415111. Epub 2014 Jul 28.
Activity-dependent changes in synaptic strength have long been postulated as cellular correlates of learning and memory. Long-term potentiation (LTP), a well characterized form of synaptic plasticity, is often expressed as an increase in the number of postsynaptic AMPA-type glutamate receptors (AMPARs). Although the precise molecular mechanisms governing LTP remain elusive, this study identifies one member of the sorting nexin family, Sorting Nexin 27 (SNX27), as a critical component in this process. The ability of sorting nexins to bind specific phospholipids as well as their propensity to form protein-protein complexes, points to a role for these proteins in membrane trafficking and protein sorting. Here, we demonstrate that SNX27 binds to AMPARs, and that this interaction is regulated in an activity-dependent manner. Furthermore, we provide evidence that SNX27 is synaptically enriched and its level of expression regulates targeting of AMPARs to the neuronal surface. Loss of SNX27 abolishes recruitment of surface AMPARs during chemical LTP. Collectively, our data suggest a role for SNX27 in modulating synaptic plasticity through regulated interaction with AMPARs.
长期以来，人们一直认为突触强度的活性依赖性变化是学习和记忆的细胞相关性。长时程增强（LTP）是一种特征明确的突触可塑性形式，通常表现为突触后 AMPA 型谷氨酸受体（AMPAR）数量的增加。尽管调节 LTP 的精确分子机制仍不清楚，但本研究确定了分选连接蛋白家族的一个成员，分选连接蛋白 27（SNX27），是该过程的关键组成部分。分选连接蛋白能够结合特定的磷脂以及形成蛋白质-蛋白质复合物的倾向，表明这些蛋白质在膜运输和蛋白质分选中发挥作用。在这里，我们证明 SNX27 与 AMPAR 结合，并且这种相互作用受到活性依赖性调节。此外，我们提供的证据表明 SNX27 在突触中富集，其表达水平调节 AMPAR 向神经元表面的靶向。SNX27 的缺失消除了化学 LTP 期间表面 AMPAR 的募集。总之，我们的数据表明 SNX27 通过与 AMPAR 的调节相互作用在调节突触可塑性中发挥作用。
