ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity
ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity
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DOI：
10.1242/dev.075366
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发表时间：
2012-01-15
期刊：
影响因子：
4.6
通讯作者：
Larsen, Melinda
中科院分区：
文献类型：
--
作者：
Daley, William P.;Gervais, Elise M.;Larsen, Melinda
基底膜对于上皮组织的组织和功能至关重要。然而，基底膜被限制在上皮组织基底周缘的机制以及调节协调组织组织的基底膜介导的信号尚不清楚。在此，我们报道，在发育中的小鼠颌下唾液腺中，Rho激酶（ROCK）通过将基底膜限制在上皮基底周边来控制协调的组织组织，并且ROCK抑制导致异位基底膜在整个上皮室中积累。 ROCK 调节的 PAR-1b (MARK2) 定位限制在外基底上皮细胞层，是基底膜定位在组织外围所必需的。 PAR-1b 是基底膜沉积所特别需要的，因为抑制 PAR-1b 激酶活性可防止基底膜沉积并破坏整个组织组织，而抑制 PAR-1b 与 ROCK 抑制一起可防止基底膜的内部积聚。相反，野生型 PAR-1b 的异位过度表达会导致异位内部基底膜沉积。值得注意的是，在 ROCK1 或 PAR-1b 抑制存在的情况下，在外源基底膜上培养唾液上皮细胞可以拯救上皮组织，而这种基底膜介导的拯救需要功能性整合素 beta 1 来维持上皮细胞与细胞的粘附。总而言之，这些研究表明 ROCK1/PAR-1b 依赖性的基底膜放置调节对于协调组织极性和发育中的下颌下唾液腺组织结构是必需的。
The basement membrane is crucial for epithelial tissue organization and function. However, the mechanisms by which basement membrane is restricted to the basal periphery of epithelial tissues and the basement membrane-mediated signals that regulate coordinated tissue organization are not well defined. Here, we report that Rho kinase (ROCK) controls coordinated tissue organization by restricting basement membrane to the epithelial basal periphery in developing mouse submandibular salivary glands, and that ROCK inhibition results in accumulation of ectopic basement membrane throughout the epithelial compartment. ROCK-regulated restriction of PAR-1b (MARK2) localization in the outer basal epithelial cell layer is required for basement membrane positioning at the tissue periphery. PAR-1b is specifically required for basement membrane deposition, as inhibition of PAR-1b kinase activity prevents basement membrane deposition and disrupts overall tissue organization, and suppression of PAR-1b together with ROCK inhibition prevents interior accumulations of basement membrane. Conversely, ectopic overexpression of wild-type PAR-1b results in ectopic interior basement membrane deposition. Significantly, culture of salivary epithelial cells on exogenous basement membrane rescues epithelial organization in the presence of ROCK1 or PAR-1b inhibition, and this basement membrane-mediated rescue requires functional integrin beta 1 to maintain epithelial cell-cell adhesions. Taken together, these studies indicate that ROCK1/PAR-1b-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland.