小柯机器人

美国德克萨斯大学圣安东尼奥健康科学中心Gek-Ming Sia研究小组发现，内源性神经元补体抑制剂SRPX2可防止发育过程中补体介导的突触消除。相关论文于2020年7月13日发表在《自然-神经科学》杂志上。

研究人员发现sushi结构域蛋白SRPX2是一种神经元表达的补体抑制剂，可调节补体依赖性突触消除。SRPX2直接与C1q结合并阻断其活性，SRPX2^-/Y小鼠会发生C3沉积增加和小胶质突触吞噬。这些小鼠还表现出突触数量短暂减少、外侧膝状核中视网膜新生轴突分离增加。在体感皮层中，SRPX2^-/Y小鼠表现出丘脑皮质突触数量减少和脊椎修剪增加。

C3^-/-;SRPX2^-/Y双敲除小鼠具有与C3^-/-小鼠相关而非SRPX2^-/Y小鼠相关的表型，这表明C3对于SRPX2介导的突触消除作用是必需的。总之，这些结果表明SRPX2保护突触免受丘脑和皮层中补体介导的消除。

据悉，补体介导的突触消除是脑发育和神经系统疾病的重要过程，但是尚不清楚神经元是否表达保护突触免受补体介导突触消除的补体抑制剂。

附：英文原文

Title: The endogenous neuronal complement inhibitor SRPX2 protects against complement-mediated synapse elimination during development

Author: Qifei Cong, Breeanne M. Soteros, Mackenna Wollet, Jun Hee Kim, Gek-Ming Sia

Issue&Volume: 2020-07-13

Abstract: Complement-mediated synapse elimination has emerged as an important process in both brain development and neurological diseases, but whether neurons express complement inhibitors that protect synapses against complement-mediated synapse elimination remains unknown. Here, we show that the sushi domain protein SRPX2 is a neuronally expressed complement inhibitor that regulates complement-dependent synapse elimination. SRPX2 directly binds to C1q and blocks its activity, and SRPX2/Y mice show increased C3 deposition and microglial synapse engulfment. They also show a transient decrease in synapse numbers and increase in retinogeniculate axon segregation in the lateral geniculate nucleus. In the somatosensory cortex, SRPX2/Y mice show decreased thalamocortical synapse numbers and increased spine pruning. C3/;SRPX2/Y double-knockout mice exhibit phenotypes associated with C3/ mice rather than SRPX2/Y mice, which indicates that C3 is necessary for the effect of SRPX2 on synapse elimination. Together, these results show that SRPX2 protects synapses against complement-mediated elimination in both the thalamus and the cortex.

DOI: 10.1038/s41593-020-0672-0

Source: https://www.nature.com/articles/s41593-020-0672-0

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex