Ca2+-PP2B-PSD-95 轴：PSD-95 丝氨酸 295 磷酸化状态的新调节机制。

Ca2+-PP2B-PSD-95 axis: A novel regulatory mechanism of the phosphorylation state of Serine 295 of PSD-95.

机构信息

Department of Basic Medical Sciences, Institute of Medical Science, Division of Neuronal Network, University of Tokyo, Tokyo, Japan.

出版信息

PLoS One. 2024 Nov 7;19(11):e0313441. doi: 10.1371/journal.pone.0313441. eCollection 2024.

DOI:10.1371/journal.pone.0313441

PMID:39509447

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11542788/

Abstract

The phosphorylation state of PSD-95 at Serine 295 (Ser295) is important for the regulation of synaptic plasticity. Although the activation of NMDA receptors (NMDARs), which initiates an intracellular calcium signaling cascade, decreases phosphorylated Ser295 (pS295) of PSD-95, the molecular mechanisms are not fully understood. We found that the calcium-activated protein phosphatase PP2B dephosphorylated pS295 not only in basal conditions but also in NMDAR-activated conditions in cultured neurons. The biochemical assay also revealed the dephosphorylation of pS295 by PP2B, consistently supporting the results obtained using neurons. The newly identified calcium signaling cascade "Ca2+-PP2B-PSD-95 axis" would play an important role in the molecular mechanism for NMDA receptor-dependent plasticity.

摘要

PSD-95 在丝氨酸 295 处的磷酸化状态（Ser295）对于调节突触可塑性很重要。尽管 NMDA 受体（NMDARs）的激活会引发细胞内钙信号级联反应，从而降低 PSD-95 的磷酸化 Ser295（pS295），但其分子机制尚不完全清楚。我们发现，钙激活的蛋白磷酸酶 PP2B 不仅在基础条件下而且在培养神经元中的 NMDAR 激活条件下使 pS295 去磷酸化。生化测定还揭示了 PP2B 对 pS295 的去磷酸化作用，这与使用神经元获得的结果一致。新鉴定的钙信号级联“Ca2+-PP2B-PSD-95 轴”在 NMDA 受体依赖性可塑性的分子机制中发挥重要作用。