Synaptic refinement is a critical physiological process that removes excess synapses to establish and maintain functional neuronal circuits. Recent studies have shown that focal exposure of phosphatidylserine (PS) on synapses acts as an “eat me” signal to mediate synaptic pruning. However, the molecular mechanism underlying PS externalization at synapses remains elusive. Here, we find that murine CDC50A, a chaperone of phospholipid flippases, localizes to synapses, and that its expression depends on neuronal activity. Cdc50a knockdown leads to phosphatidylserine exposure at synapses and subsequent erroneous synapse removal by microglia partly via the GPR56 pathway. Taken together, our data support that CDC50A safeguards synapse maintenance by regulating focal phosphatidylserine exposure at synapses.

中文翻译：

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磷脂翻转酶伴侣 CDC50A 是通过调节磷脂酰丝氨酸暴露来维持突触所必需的


突触细化是一个关键的生理过程，它去除多余的突触以建立和维持功能性神经元回路。最近的研究表明，突触上磷脂酰丝氨酸（PS）的局部暴露可以作为“吃我”信号来介导突触修剪。然而，突触 PS 外化的分子机制仍然难以捉摸。在这里，我们发现鼠类 CDC50A（磷脂翻转酶的伴侣）定位于突触，并且其表达取决于神经元活动。 Cdc50a 敲低导致突触处磷脂酰丝氨酸暴露，随后小胶质细胞部分通过 GPR56 途径错误地去除突触。综上所述，我们的数据支持 CDC50A 通过调节突触处的局灶性磷脂酰丝氨酸暴露来保障突触维持。