Department of Cellular and Physiological Sciences, University of British Columbia, Life Sciences Institute, Vancouver, BC, Canada.
Dev Dyn. 2011 Jan;240(1):36-51. doi: 10.1002/dvdy.22488.
Cell adhesion must be precisely regulated to enable both dynamic morphogenetic processes and the subsequent transition to stable tissue maintenance. Integrins link the intracellular cytoskeleton and extracellular matrix, relaying bidirectional signals across the plasma membrane. In vitro studies have demonstrated that multiple mechanisms control integrin-mediated adhesion; however, their roles during development are poorly understood. We used mutations that activate or deactivate specific functions of vertebrate β-integrins in vitro to investigate how perturbing Drosophila βPS-integrin regulation in developing embryos regulation affects tissue morphogenesis and maintenance. We found that morphogenetic processes use various β-integrin regulatory mechanisms to differing degrees and that conformational changes associated with outside-in activation are essential for developmental integrin functions. Long-term adhesion is also sensitive to integrin dysregulation, suggesting integrins must be continuously regulated to support stable tissue maintenance. Altogether, in vivo phenotypic analyses allowed us to identify the importance of various β-integrin regulatory mechanisms during different morphogenetic processes.
细胞黏附必须精确调控，以实现动态形态发生过程和随后向稳定组织维持的转变。整合素将细胞内细胞骨架与细胞外基质连接起来，在质膜两侧传递双向信号。体外研究表明，多种机制控制着整合素介导的黏附；然而，其在发育过程中的作用还知之甚少。我们使用突变激活或失活脊椎动物β整合素的特定功能，在体外研究扰乱果蝇βPS-整合素调控如何影响发育胚胎组织形态发生和维持。我们发现形态发生过程以不同程度使用各种β整合素调控机制，并且与外向激活相关的构象变化对于发育整合素功能是必需的。长期黏附也对整合素调控失调敏感，这表明整合素必须持续调控以支持稳定的组织维持。总的来说，体内表型分析使我们能够确定各种β整合素调控机制在不同形态发生过程中的重要性。
