Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States.
Huffington Center on Aging, Baylor College of Medicine, Houston, TX, United States.
Front Neural Circuits. 2020 Oct 16;14:583391. doi: 10.3389/fncir.2020.583391. eCollection 2020.
During development, neurons generate excess processes which are then eliminated in concert with circuit maturation. C1q is the initiating protein in the complement cascade and has been implicated in this process, but whether C1q-mediated elimination is targeted to particular neural compartments is unclear. Using the murine retina, we identify C1q as a specific regulator of horizontal cell neurite confinement. Subsets of horizontal cell dendritic and axonal neurites extend into the outer retina suggesting that complement achieves both cellular and subcellular selectivity. These alterations emerge as outer retina synapses become mature. expression is restricted to retina microglia, and the loss of C1q results in decreased microglia activation. This pathway appears independent of the C3a receptor (C3aR) and complement receptor 3 (CR3), as horizontal cells are normal when either protein is absent. Together, these data identify a new role for C1q in cell and neurite-specific confinement and implicate microglia-mediated phagocytosis in this process.
在发育过程中，神经元会产生多余的突起，然后在与回路成熟的同时被消除。C1q 是补体级联反应的起始蛋白，并与该过程有关，但 C1q 介导的消除是否针对特定的神经区室尚不清楚。利用鼠类视网膜，我们确定 C1q 是水平细胞突起限制的特定调节剂。水平细胞树突和轴突突起的亚群延伸到外视网膜，表明补体具有细胞和亚细胞选择性。这些变化在外突突触成熟时出现。在视网膜小胶质细胞中表达受限，C1q 的缺失导致小胶质细胞激活减少。该途径似乎独立于 C3a 受体 (C3aR) 和补体受体 3 (CR3)，因为当缺失任何一种蛋白时，水平细胞均正常。综上所述，这些数据确定了 C1q 在细胞和突起特异性限制中的新作用，并表明小胶质细胞介导的吞噬作用参与了这一过程。
