The γ-Protocadherins Interact Physically and Functionally with Neuroligin-2 to Negatively Regulate Inhibitory Synapse Density and Are Required for Normal Social Interaction.
The γ-Protocadherins Interact Physically and Functionally with Neuroligin-2 to Negatively Regulate Inhibitory Synapse Density and Are Required for Normal Social Interaction.
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γ-Protocadherins与神经连接蛋白-2在物理和功能上相互作用，负向调节抑制性突触密度，是正常社会互动所必需的。
DOI：
10.1007/s12035-020-02263-z
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发表时间：
2021-06
影响因子：
5.1
通讯作者：
Weiner JA
中科院分区：
文献类型：
--
作者：
Steffen DM;Ferri SL;Marcucci CG;Blocklinger KL;Molumby MJ;Abel T;Weiner JA
细胞粘附分子（CAM）是发育过程中神经回路形成的关键参与者。γ-原钙粘素（γ-Protocadherins，γ-Pcdhs）是由Pcdhg基因簇编码的22种CAM家族，在树突分支、轴突靶向和突触发育中发挥重要作用。我们先前表明，多种γ-Pcdhs与自闭症相关的CAM Neuroligin-1发生物理相互作用，并抑制后者促进兴奋性突触成熟的能力。在这里，我们发现γ-Pcdh也可以与相关的Neuroligin-2发生物理相互作用，并抑制CAM促进抑制性突触发育的能力。在人工突触测定中，在非神经元细胞中与Neuroligin-2共表达的γ-Pcdhs减少接触海马轴突的抑制性突触前成熟。缺乏来自前脑（包括皮质、海马和杏仁核的部分）的γ-Pcdhs的小鼠表现出增加的抑制性突触密度和增加的体内神经配素-2与抑制性突触后标记物的共定位。这些Pcdhg突变体也表现出有缺陷的社会联系和焦虑样表型的行为测定。总之，这些结果表明，γ-Pcdhs负调节神经连接素，以限制突触密度的方式，这对正常行为是重要的。
Cell adhesion molecules (CAMs) are key players in the formation of neural circuits during development. The γ-protocadherins (γ-Pcdhs), a family of 22 CAMs encoded by the Pcdhg gene cluster, are known to play important roles in dendrite arborization, axon targeting, and synapse development. We showed previously that multiple γ-Pcdhs interact physically with the autism-associated CAM Neuroligin-1, and inhibit the latter’s ability to promote excitatory synapse maturation. Here, we show that γ-Pcdh can also interact physically with the related Neuroligin-2, and inhibit this CAM’s ability to promote inhibitory synapse development. In an artificial synapse assay, γ-Pcdhs co-expressed with Neuroligin-2 in non-neuronal cells reduce inhibitory presynaptic maturation in contacting hippocampal axons. Mice lacking the γ-Pcdhs from the forebrain (including the cortex, the hippocampus, and portions of the amygdala) exhibit increased inhibitory synapse density and increased co-localization of Neuroligin-2 with inhibitory postsynaptic markers in vivo. These Pcdhg mutants also exhibit defective social affiliation and an anxiety-like phenotype in behavioral assays. Together, these results suggest that γ-Pcdhs negatively regulate Neuroligins to limit synapse density in a manner that is important for normal behavior.
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DOI：
10.1002/ar.21318
发表时间：
2011-10
影响因子：
2
作者：
Fairless, Andrew H.;Shah, Rhia Y.;Guthrie, Ashley J.;Li, Hongzhe;Brodkin, Edward S.
通讯作者：
Brodkin, Edward S.
影响因子：
4.8
作者：
Hasegawa S;Kobayashi H;Kumagai M;Nishimaru H;Tarusawa E;Kanda H;Sanbo M;Yoshimura Y;Hirabayashi M;Hirabayashi T;Yagi T
通讯作者：
Yagi T
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.2
作者：
Elegheert J;Cvetkovska V;Clayton AJ;Heroven C;Vennekens KM;Smukowski SN;Regan MC;Jia W;Smith AC;Furukawa H;Savas JN;de Wit J;Begbie J;Craig AM;Aricescu AR
通讯作者：
Aricescu AR
影响因子：
14.8
作者：
Biederer, Thomas;Scheiffele, Peter
通讯作者：
Scheiffele, Peter