Chowdhury Dhrubajyoti, Hell Johannes W
Department of Pharmacology, University of California, Davis, Davis, CA, United States.
Front Synaptic Neurosci. 2019 Mar 12;11:6. doi: 10.3389/fnsyn.2019.00006. eCollection 2019.
AMPA-type glutamate receptors (AMPARs) are clustered into functional nanodomains at postsynaptic sites through anchorage by the scaffolding protein, postsynaptic density protein-95 (PSD-95). The synaptic abundance of AMPARs is dynamically controlled in various forms of synaptic plasticity. Removal of AMPARs from the synapse in long-term depression (LTD) requires mobilization of PSD-95 away from the synapse. The molecular mechanisms underlying PSD-95 dispersal from the synapse during LTD are not completely understood. Here we show that, following Ca influx, binding of Ca/calmodulin (CaM) to PSD-95 triggers loss of synaptic PSD-95 as well as surface AMPARs during chemically induced LTD in cultured rat neurons. Our data suggest that a reduction in PSD-95 palmitoylation mediates the effect of Ca/CaM on PSD-95 synaptic levels during LTD. These findings reveal a novel molecular mechanism for synaptic AMPAR regulation in LTD.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体（AMPARs）通过与支架蛋白突触后致密蛋白95（PSD-95）锚定，在突触后位点聚集成功能性纳米结构域。AMPARs的突触丰度在各种形式的突触可塑性中受到动态调控。在长时程抑制（LTD）中，从突触中移除AMPARs需要PSD-95从突触中动员出来。LTD期间PSD-95从突触中分散的分子机制尚未完全阐明。在这里，我们表明，在钙离子内流后，钙/钙调蛋白（CaM）与PSD-95的结合会在化学诱导的培养大鼠神经元LTD过程中引发突触PSD-95以及表面AMPARs的丢失。我们的数据表明，PSD-95棕榈酰化的减少介导了Ca/CaM对LTD期间PSD-95突触水平的影响。这些发现揭示了LTD中突触AMPAR调节的一种新的分子机制。
