E-Cadherin/HMR-1 Membrane Enrichment Is Polarized by WAVE-Dependent Branched Actin.
E-Cadherin/HMR-1 Membrane Enrichment Is Polarized by WAVE-Dependent Branched Actin.
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DOI：
10.3390/jdb9020019
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发表时间：
2021-05-07
影响因子：
2.7
通讯作者：
Soto MC
中科院分区：
文献类型：
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作者：
Cordova-Burgos L;Patel FB;Soto MC
极化的上皮细胞在与顶端F-肌动蛋白带相连的顶端连接处相互粘连。顶端连接的调节重塑支持形态发生，而失调的重塑促进癌症等疾病。我们已经证明，在线虫胚胎连接的发育过程中，分支肌动蛋白调节蛋白WAVE和顶端连接蛋白Cherin组装在一起。如果波在胚胎上皮细胞中缺失，过多的钙粘附素聚集在顶膜，而顶端的F-肌动蛋白减少，这表明过剩的钙粘附素功能不完全。我们认为，波通过调节细胞膜上钙粘连蛋白的动态积聚来支持顶端连接。为了测试这个模型，我们在这里检查在成熟的上皮细胞，即胚胎后的线虫肠道中，是否需要波来丰富钙粘附素的膜和顶端-基底极性。我们发现，幼虫和成虫的肠道具有不同的钙粘连蛋白群体，每个群体都对波分支肌动蛋白有不同的依赖关系。活体成像显示，波成分的丢失改变了胚胎后E-钙粘素膜的丰富，特别是在顶侧区域，并改变了侧膜。对PI(4，5)P2生物传感器的分析表明，波或钙粘附素的丢失改变了上皮膜的极性。EM(电子显微镜)显示包括分离在内的侧膜变化。这些发现对理解WAVE和钙粘附素的突变如何改变细胞极性具有重要意义。
Polarized epithelial cells adhere to each other at apical junctions that connect to the apical F-actin belt. Regulated remodeling of apical junctions supports morphogenesis, while dysregulated remodeling promotes diseases such as cancer. We have documented that branched actin regulator, WAVE, and apical junction protein, Cadherin, assemble together in developing C. elegans embryonic junctions. If WAVE is missing in embryonic epithelia, too much Cadherin assembles at apical membranes, and yet apical F-actin is reduced, suggesting the excess Cadherin is not fully functional. We proposed that WAVE supports apical junctions by regulating the dynamic accumulation of Cadherin at membranes. To test this model, here we examine if WAVE is required for Cadherin membrane enrichment and apical–basal polarity in a maturing epithelium, the post-embryonic C. elegans intestine. We find that larval and adult intestines have distinct apicobasal populations of Cadherin, each with distinct dependence on WAVE branched actin. In vivo imaging shows that loss of WAVE components alters post-embryonic E-cadherin membrane enrichment, especially at apicolateral regions, and alters the lateral membrane. Analysis of a biosensor for PI(4,5)P2 suggests loss of WAVE or Cadherin alters the polarity of the epithelial membrane. EM (electron microscopy) illustrates lateral membrane changes including separations. These findings have implications for understanding how mutations in WAVE and Cadherin may alter cell polarity.