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首都医科大学 副校长 Capital Medical University
教授 Professor
张晨博士,首都医科大学教授、博士生导师,党委常委、副校长,兼研究生院院长、首都医科大学基础医学国家级实验教学示范中心主任;兼任国务院学位委员会第八届学科评议组成员、转化医学与创新药物国家重点实验室副主任、北京市神经再生修复研究重点实验室主任、中国生物物理学会理事、中国实验动物学会理事、中国神经科学学会理事、北京神经科学学会副理事长等。承担国家重点研发计划(首席科学家)、国家杰出青年基金、优青、国自然重大研究计划-集成项目、教育部“新世纪优秀人才支持计划”等,获国家级百千万人才工程、国家有突出贡献中青年专家、国务院享受政府特殊津贴人员、北京市优秀教育工作者、中华医学科技奖-青年科技奖、全国百篇优秀博士论文奖等,作为院长率领首医基础医学院获“全国教育系统优秀集体”等
报告题目:
Rabphilin-3A undergoes phase separation to regulate GluN2A mobility and surface clustering
报告摘要:
N-甲基-D-天冬氨酸受体(NMDAR)对兴奋性神经传递和突触可塑性是必不可少的。GluN2A和GluN2B是NMDAR的两个主要亚基,在突触和突触外部位表现出不同的簇状分布模式和移动性。然而,GluN2A簇是如何具体组织和稳定的仍然知之甚少。在这里,我们发现以前报道的GluN2A特异性结合伙伴RabPhilin-3A(Rph3A)具有相分离的能力,这依赖于其N-末端结构域中的精氨酸残基。Rph3A相分离通过结合GluN2A的C-末端结构域促进GluN2A的聚集。Rph3A、GluN2A和支架蛋白PSD95形成的复合体促进了Rph3A的相分离。破坏Rph3A的相分离抑制了突触和突触外表面聚集、突触定位、稳定性和突触反应。综上所述,我们的结果揭示了Rph3A相分离在决定GluN2A在神经元表面的组织和稳定性方面的关键作用。
N-methyl-D-aspartate receptors (NMDARs) are essential for excitatory neurotransmission and synaptic plasticity. GluN2A and GluN2B, two predominant Glu2N subunits of NMDARs in the hippocampus and the cortex, display distinct clustered distribution patterns and mobility at synaptic and extrasynaptic sites. However, how GluN2A clusters are specifically organized and stabilized remains poorly understood. Here, we found that the previously reported GluN2A-specific binding partner Rabphilin-3A (Rph3A) has the ability to undergo phase separation, which relies on arginine residues in its N-terminal domain. Rph3A phase separation promotes GluN2A clustering by binding GluN2A’s C-terminal domain. A complex formed by Rph3A, GluN2A, and the scaffolding protein PSD95 promoted Rph3A phase separation. Disrupting Rph3A’s phase separation suppressed the synaptic and extrasynaptic surface clustering, synaptic localization, stability, and synaptic response of GluN2A in hippocampal neurons. Together, our results reveal the critical role of Rph3A phase separation in determining the organization and stability of GluN2A in the neuronal surface.
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张晨博士,首都医科大学教授、博士生导师,党委常委、副校长,兼研究生院院长、首都医科大学基础医学国家级实验教学示范中心主任;兼任国务院学位委员会第八届学科评议组成员、转化医学与创新药物国家重点实验室副主任、北京市神经再生修复研究重点实验室主任、中国生物物理学会理事、中国实验动物学会理事、中国神经科学学会理事、北京神经科学学会副理事长等。承担国家重点研发计划(首席科学家)、国家杰出青年基金、优青、国自然重大研究计划-集成项目、教育部“新世纪优秀人才支持计划”等,获国家级百千万人才工程、国家有突出贡献中青年专家、国务院享受政府特殊津贴人员、北京市优秀教育工作者、中华医学科技奖-青年科技奖、全国百篇优秀博士论文奖等,作为院长率领首医基础医学院获“全国教育系统优秀集体”等
报告题目:
Rabphilin-3A undergoes phase separation to regulate GluN2A mobility and surface clustering
报告摘要:
N-甲基-D-天冬氨酸受体(NMDAR)对兴奋性神经传递和突触可塑性是必不可少的。GluN2A和GluN2B是NMDAR的两个主要亚基,在突触和突触外部位表现出不同的簇状分布模式和移动性。然而,GluN2A簇是如何具体组织和稳定的仍然知之甚少。在这里,我们发现以前报道的GluN2A特异性结合伙伴RabPhilin-3A(Rph3A)具有相分离的能力,这依赖于其N-末端结构域中的精氨酸残基。Rph3A相分离通过结合GluN2A的C-末端结构域促进GluN2A的聚集。Rph3A、GluN2A和支架蛋白PSD95形成的复合体促进了Rph3A的相分离。破坏Rph3A的相分离抑制了突触和突触外表面聚集、突触定位、稳定性和突触反应。综上所述,我们的结果揭示了Rph3A相分离在决定GluN2A在神经元表面的组织和稳定性方面的关键作用。
N-methyl-D-aspartate receptors (NMDARs) are essential for excitatory neurotransmission and synaptic plasticity. GluN2A and GluN2B, two predominant Glu2N subunits of NMDARs in the hippocampus and the cortex, display distinct clustered distribution patterns and mobility at synaptic and extrasynaptic sites. However, how GluN2A clusters are specifically organized and stabilized remains poorly understood. Here, we found that the previously reported GluN2A-specific binding partner Rabphilin-3A (Rph3A) has the ability to undergo phase separation, which relies on arginine residues in its N-terminal domain. Rph3A phase separation promotes GluN2A clustering by binding GluN2A’s C-terminal domain. A complex formed by Rph3A, GluN2A, and the scaffolding protein PSD95 promoted Rph3A phase separation. Disrupting Rph3A’s phase separation suppressed the synaptic and extrasynaptic surface clustering, synaptic localization, stability, and synaptic response of GluN2A in hippocampal neurons. Together, our results reveal the critical role of Rph3A phase separation in determining the organization and stability of GluN2A in the neuronal surface.