Division of Cell and Developmental Biology, The University of Queensland, St Lucia, Queensland, Australia, 4072.
Institute of Complex Systems and Mathematical Biology, University of Aberdeen, Aberdeen, United Kingdom, AB24 3UE.
Mol Biol Cell. 2020 Nov 1;31(23):2557-2569. doi: 10.1091/mbc.E20-01-0084. Epub 2020 Sep 9.
Epithelia can eliminate apoptotic cells by apical extrusion. This is a complex morphogenetic event where expulsion of the apoptotic cell is accompanied by rearrangement of its immediate neighbors to form a rosette. A key mechanism for extrusion is constriction of an actomyosin network that neighbor cells form at their interface with the apoptotic cell. Here we report a complementary process of cytoskeletal relaxation that occurs when cortical contractility is down-regulated at the junctions between those neighbor cells themselves. This reflects a mechanosensitive Src family kinase (SFK) signaling pathway that is activated in neighbor cells when the apoptotic cell relaxes shortly after injury. Inhibiting SFK signaling blocks both the expulsion of apoptotic cells and the rosette formation among their neighbor cells. This reveals the complex pattern of spatially distinct contraction and relaxation that must be established in the neighboring epithelium for apoptotic cells to be extruded.
上皮细胞可以通过顶端挤出的方式消除凋亡细胞。这是一个复杂的形态发生事件,在这个过程中,凋亡细胞的排出伴随着其邻近细胞的重新排列,形成玫瑰花结。挤出的一个关键机制是肌动球蛋白网络的收缩,邻近细胞在与凋亡细胞的界面处形成该网络。在这里,我们报告了一个补充过程,即当这些邻近细胞自身之间的连接的皮质收缩性被下调时,细胞骨架发生松弛。这反映了一种机械敏感性 Src 家族激酶(SFK)信号通路,当凋亡细胞在受伤后不久松弛时,该通路在邻近细胞中被激活。抑制 SFK 信号通路会阻止凋亡细胞的排出以及它们的邻近细胞之间玫瑰花结的形成。这揭示了凋亡细胞被挤出时,邻近上皮细胞中必须建立的空间上明显的收缩和松弛的复杂模式。