P115 RhoGEF and microtubules decide the direction apoptotic cells extrude from an epithelium.
P115 RhoGEF and microtubules decide the direction apoptotic cells extrude from an epithelium.
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DOI：
10.1083/jcb.200903079
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发表时间：
2009-09-07
期刊：
影响因子：
--
通讯作者：
Rosenblatt J
中科院分区：
文献类型：
--
作者：
Slattum G;McGee KM;Rosenblatt J
微管和肌动蛋白/肌球蛋白网络之间的通讯决定上皮细胞的挤出极性。为了保护上皮屏障功能，垂死的细胞通过“凋亡细胞挤出”被从上皮中挤出。具体来说，注定要凋亡的细胞向其邻近的活上皮细胞发出信号，形成并收缩肌动蛋白和肌球蛋白 II 环，将垂死的细胞从上皮层中挤出。尽管大多数凋亡细胞从顶部突出，但我们发现有些细胞从底部退出。肌动蛋白和肌球蛋白 IIA 收缩的定位决定了挤压方向：基底挤压需要邻近细胞在其顶端进行圆周收缩，而顶端挤压也需要沿着基底外侧表面向下收缩。为了从基底外侧激活肌动蛋白/肌球蛋白，邻近细胞中的微管重新定向并将 p115 RhoGEF 定位到该位点。防止微管重新定向会限制顶端的收缩，从而驱动基部的挤压。挤压极性对于细胞凋亡被阻止但挤压却未被阻止的肿瘤具有重要意义，因为基底挤压可以使这些细胞启动转移。
Communication between microtubules and actin/myosin networks determine epithelial cell extrusion polarity. To preserve epithelial barrier function, dying cells are squeezed out of an epithelium by “apoptotic cell extrusion.” Specifically, a cell destined for apoptosis signals its live neighboring epithelial cells to form and contract a ring of actin and myosin II that squeezes the dying cell out of the epithelial sheet. Although most apoptotic cells extrude apically, we find that some exit basally. Localization of actin and myosin IIA contraction dictates the extrusion direction: basal extrusion requires circumferential contraction of neighboring cells at their apices, whereas apical extrusion also requires downward contraction along the basolateral surfaces. To activate actin/myosin basolaterally, microtubules in neighboring cells reorient and target p115 RhoGEF to this site. Preventing microtubule reorientation restricts contraction to the apex, driving extrusion basally. Extrusion polarity has important implications for tumors where apoptosis is blocked but extrusion is not, as basal extrusion could enable these cells to initiate metastasis.
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