Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Genetics. 2024 Aug 7;227(4). doi: 10.1093/genetics/iyae101.
To survive daily damage, the formation of actomyosin ring at the wound edge is required to rapidly close cell wounds. Calcium influx is one of the start signals for these cell wound repair events. Here, we find that the rapid recruitment of all 3 Drosophila calcium-responding and phospholipid-binding Annexin proteins (AnxB9, AnxB10, and AnxB11) to distinct regions around the wound is regulated by the quantity of calcium influx rather than their binding to specific phospholipids. The distinct recruitment patterns of these Annexins regulate the subsequent recruitment of RhoGEF2 and RhoGEF3 through actin stabilization to form a robust actomyosin ring. Surprisingly, while the wound does not close in the absence of calcium influx, we find that reduced calcium influx can still initiate repair processes, albeit leading to severe repair phenotypes. Thus, our results suggest that, in addition to initiating repair events, the quantity of calcium influx is important for precise Annexin spatiotemporal protein recruitment to cell wounds and efficient wound repair.
为了应对日常损伤，需要在伤口边缘形成肌动球蛋白环来快速封闭细胞伤口。钙离子内流是这些细胞伤口修复事件的起始信号之一。在这里，我们发现 3 种果蝇钙反应性和磷脂结合膜联蛋白蛋白（AnxB9、AnxB10 和 AnxB11）迅速募集到伤口周围特定区域的过程受到钙离子内流数量的调节，而不是受它们与特定磷脂的结合所调节。这些膜联蛋白的不同募集模式调节 RhoGEF2 和 RhoGEF3 的随后募集，通过肌动蛋白稳定形成一个强大的肌动球蛋白环。令人惊讶的是，虽然在没有钙离子内流的情况下伤口不会闭合，但我们发现减少钙离子内流仍然可以启动修复过程，尽管会导致严重的修复表型。因此，我们的结果表明，除了启动修复事件外，钙离子内流的数量对于精确的膜联蛋白时空蛋白募集到细胞伤口和有效伤口修复也很重要。
