Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells
Calcium sparks enhance the tissue fluidity within epithelial layers and promote apical extrusion of transformed cells
复制标题
钙火花增强上皮层内的组织流动性并促进转化细胞的顶端挤出
DOI：
10.1016/j.celrep.2022.111078
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发表时间：
2022
期刊：
影响因子：
8.8
通讯作者：
Fujita Y
中科院分区：
文献类型：
--
作者：
Kuromiya K;Aoki K;Ishibashi K;Yotabun M;Sekai M;Tanimura N;Iijima S;Ishikawa S;Kamasaki T;Akieda Y;Ishitani T;Hayashi T;Toda S;Yokoyama K;Lee CG;Usami I;Inoue H;Takigawa I;Gauquelin E;Sugimura K;Hino N;Fujita Y
在脊椎动物中，新出现的转化细胞通常是通过与周围正常的上皮细胞竞争而从上皮层顶部挤出的。然而，潜在的分子机制仍然难以捉摸。在这里，使用磷酸化SILAC筛选，我们发现在RasV12细胞诱导RasV12表达后不久，AHNAK2的磷酸化水平在RasV12细胞附近的正常细胞中升高，这是由钙依赖的蛋白激酶C介导的。此外，在RasV12细胞周围的正常细胞中经常发生瞬时的细胞内钙电涌，我们称之为钙火花，这是由膜拉伸时机械敏感的钙通道TRPC1介导的。然后，钙火花通过AHNAK2的磷酸化促进正常和RasV12细胞的细胞运动，并促进根尖挤出。此外，类似的钙火花也正向调节斑马鱼幼体中RasV12转化细胞的顶端挤出。因此，在细胞竞争的早期阶段，钙火花在消除转化细胞方面起着至关重要的作用。
In vertebrates, newly emerging transformed cells are often apically extruded from epithelial layers through cell competition with surrounding normal epithelial cells. However, the underlying molecular mechanism remains elusive. Here, using phospho-SILAC screening, we show that phosphorylation of AHNAK2 is elevated in normal cells neighboring RasV12 cells soon after the induction of RasV12 expression, which is mediated by calcium-dependent protein kinase C. In addition, transient upsurges of intracellular calcium, which we call calcium sparks, frequently occur in normal cells neighboring RasV12 cells, which are mediated by mechanosensitive calcium channel TRPC1 upon membrane stretching. Calcium sparks then enhance cell movements of both normal and RasV12 cells through phosphorylation of AHNAK2 and promote apical extrusion. Moreover, comparable calcium sparks positively regulate apical extrusion of RasV12-transformed cells in zebrafish larvae as well. Hence, calcium sparks play a crucial role in the elimination of transformed cells at the early phase of cell competition.