EB1-recruited microtubule +TIP complexes coordinate protrusion dynamics during 3D epithelial remodeling.
EB1-recruited microtubule +TIP complexes coordinate protrusion dynamics during 3D epithelial remodeling.
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DOI：
10.1016/j.cub.2012.02.069
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发表时间：
2012-05-08
期刊：
影响因子：
9.2
通讯作者：
Wittmann, Torsten
中科院分区：
文献类型：
--
作者：
Gierke, Sarah;Wittmann, Torsten
上皮细胞的重塑，即顶端-基底极化细胞转变为迁移表型，在多细胞生物体的发育和疾病中起着核心作用。虽然动态微管（MT）需要在平坦表面上定向迁移，MT动力学如何控制或有助于在更生理的三维（3D）环境中的上皮重塑尚不清楚。我们使用共聚焦活细胞成像分析MT功能和动态过程中的3D上皮形态发生和重塑极化的Madin-Darby犬肾（MDCK）上皮细胞进行部分上皮间质转化（EMT），在响应肝细胞生长因子（HGF）。我们发现，肝细胞生长因子治疗增加MT的生长速度之前，形态学变化是明显的，大量的MT生长成肝细胞生长因子诱导的细胞扩展独立的中心体重新定位。使用慢病毒介导的shRNA，我们证明，EB 1，一个衔接蛋白，介导的招聘许多其他+TIP蛋白的不断增长的MT加结束，是需要这个HGF诱导的MT重组。我们进一步表明，突起和粘附动力学是混乱的，并且在EB 1耗尽的细胞中，到HGF诱导的细胞延伸的尖端的囊泡运输被破坏。我们的结论是，EB 1介导的相互作用与不断增长的MT是重要的协调细胞形状的变化和定向迁移到周围的细胞外基质上皮重塑过程中的生理三维环境。相反，EB 1是不需要建立或维持的顶-基底细胞极性，表明不同类型的细胞极性+TIPs和MT的不同功能。
Epithelial remodeling, in which apical-basal polarized cells switch to a migratory phenotype, plays a central role in development and disease of multicellular organisms. Although dynamic microtubules (MTs) are required for directed migration on flat surfaces, how MT dynamics are controlled or contribute to epithelial remodeling in a more physiological three-dimensional (3D) environment is not understood. We use confocal live cell imaging to analyze MT function and dynamics during 3D epithelial morphogenesis and remodeling of polarized Madin-Darby canine kidney (MDCK) epithelial cells that undergo partial epithelial-to-mesenchymal transition (EMT) in response to hepatocyte growth factor (HGF). We find that HGF treatment increases MT growth rate before morphological changes are evident, and that large numbers of MTs grow into HGF-induced cell extensions independent of centrosome reorientation. Using lentivirus-mediated shRNA, we demonstrate that EB1, an adaptor protein that mediates recruitment of numerous other +TIP proteins to growing MT plus ends, is required for this HGF-induced MT reorganization. We further show that protrusion and adhesion dynamics are disorganized, and that vesicular trafficking to the tip of HGF-induced cell extensions is disrupted in EB1-depleted cells. We conclude that EB1-mediated interactions with growing MTs are important to coordinate cell shape changes and directed migration into the surrounding extracellular matrix during epithelial remodeling in a physiological 3D environment. In contrast, EB1 is not required for the establishment or maintenance of apical-basal cell polarity, suggesting different functions of +TIPs and MTs in different types of cell polarity.
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影响因子：
9.2
作者：
Kwon, Sang-Ho;Nedvetsky, Pavel I.;Mostov, Keith E.
通讯作者：
Mostov, Keith E.
影响因子：
4
作者：
Prigozhina, Natalie L.;Waterman-Storer, Clare M.
通讯作者：
Waterman-Storer, Clare M.
DOI：
10.1083/jcb.200405094
发表时间：
2005-01-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mimori-Kiyosue Y;Grigoriev I;Lansbergen G;Sasaki H;Matsui C;Severin F;Galjart N;Grosveld F;Vorobjev I;Tsukita S;Akhmanova A
通讯作者：
Akhmanova A
动态微管对细胞迁移的调节。
影响因子：
7.3
作者：
Kaverina, Irina;Straube, Anne
通讯作者：
Straube, Anne
影响因子：
48
作者：
Riedl, Julia;Crevenna, Alvaro H.;Wedlich-Soldner, Roland
通讯作者：
Wedlich-Soldner, Roland