Neurexin-3 subsynaptic densities are spatially distinct from Neurexin-1 and essential for excitatory synapse nanoscale organization in the hippocampus.
Neurexin-3 subsynaptic densities are spatially distinct from Neurexin-1 and essential for excitatory synapse nanoscale organization in the hippocampus.
复制标题
DOI：
10.1038/s41467-023-40419-2
复制
发表时间：
2023-08-05
影响因子：
16.6
通讯作者：
Aoto, Jason
中科院分区：
文献类型：
--
作者：
Lloyd, Brian A.;Han, Ying;Roth, Rebecca;Zhang, Bo;Aoto, Jason
突触传递的关键蛋白质是不均匀分布和组装成高密度的区域，称为突触下密度（SSD），跨突触排列在纳米柱中。Neurexin-1和neurexin-3是必需的突触前粘附分子，其分别通过与不同的突触后配体的跨突触相互作用非冗余地控制NMDAR和AMPAR介导的突触传递。尽管它们具有功能相关性，但有关单个神经毒素的纳米级特性、它们对兴奋性突触的突触下组织的影响以及控制单个神经毒素如何参与精确跨突触相互作用的机制的基本问题尚不清楚。使用双受阻3D dSTORM和neurexin小鼠模型，我们将neurexin-3鉴定为调节海马中兴奋性突触纳米组织的关键突触前粘附分子。此外，内源性neurexin-1和neurexin-3形成离散和非重叠的SSD，其相对于其突触后配体富集。因此，neurexin-1和neurexin-3的纳米级组织可以解释单个neurexin如何并行地发出信号以控制不同的突触特性。单个神经毒素如何控制不同的突触特性？在这里，作者证明了Nrxn 1和Nrxn 3的纳米级特性是空间离散的，并提出了一个模型，其中Nrxn 1和Nrxn 3并行发送信号以控制突触功能。
Proteins critical for synaptic transmission are non-uniformly distributed and assembled into regions of high density called subsynaptic densities (SSDs) that transsynaptically align in nanocolumns. Neurexin-1 and neurexin-3 are essential presynaptic adhesion molecules that non-redundantly control NMDAR- and AMPAR-mediated synaptic transmission, respectively, via transsynaptic interactions with distinct postsynaptic ligands. Despite their functional relevance, fundamental questions regarding the nanoscale properties of individual neurexins, their influence on the subsynaptic organization of excitatory synapses and the mechanisms controlling how individual neurexins engage in precise transsynaptic interactions are unknown. Using Double Helix 3D dSTORM and neurexin mouse models, we identify neurexin-3 as a critical presynaptic adhesion molecule that regulates excitatory synapse nano-organization in hippocampus. Furthermore, endogenous neurexin-1 and neurexin-3 form discrete and non-overlapping SSDs that are enriched opposite their postsynaptic ligands. Thus, the nanoscale organization of neurexin-1 and neurexin-3 may explain how individual neurexins signal in parallel to govern different synaptic properties. How do individual neurexins control distinct synaptic properties? Here, the authors show that the nanoscopic properties of Nrxn1 and Nrxn3 are spatially discrete and propose a model where Nrxn1 and Nrxn3 signal in parallel to control synapse function.
登录
查看更多内容
影响因子：
16.2
作者：
Dani, Adish;Huang, Bo;Bergan, Joseph;Dulac, Catherine;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
25
作者：
Aoto, Jason;Foeldy, Csaba;Ilcus, Silviana Maria Ciurea;Tabuchi, Katsuhiko;Suedhof, Thomas C.
通讯作者：
Suedhof, Thomas C.
影响因子：
8.8
作者：
Boxer EE;Seng C;Lukacsovich D;Kim J;Schwartz S;Kennedy MJ;Földy C;Aoto J
通讯作者：
Aoto J
影响因子：
21.3
作者：
Gong, Liang-Wei;Alvarez de Toledo, Guillermo;Lindau, Manfred
通讯作者：
Lindau, Manfred
影响因子：
3.7
作者：
Freche D;Pannasch U;Rouach N;Holcman D
通讯作者：
Holcman D