Polarization of the epithelial layer and apical localization of integrins are required for engulfment of apoptotic cells in the Drosophila ovary.
Polarization of the epithelial layer and apical localization of integrins are required for engulfment of apoptotic cells in the Drosophila ovary.
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DOI：
10.1242/dmm.021998
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发表时间：
2015-12
影响因子：
4.3
通讯作者：
McCall K
中科院分区：
文献类型：
--
作者：
Meehan TL;Kleinsorge SE;Timmons AK;Taylor JD;McCall K
上皮细胞对死细胞或碎片的无效清除可导致或加剧衰弱性病症，如色素性视网膜炎、黄斑变性、慢性阻塞性肺病和哮喘。尽管被上皮细胞吞噬的重要性，但对这些细胞内所需的分子变化知之甚少。整合素的失调以前与疾病状态有关，这表明更好地理解受体运输的调节可能是治疗由吞噬缺陷引起的疾病的关键。在这里，我们证明了整合素异源二聚体α PS 3/βPS变得顶端富集，并需要被果蝇卵巢上皮滤泡细胞吞噬。我们发现整合素异源二聚体的定位和功能在很大程度上由α亚基指导。此外，适当的细胞极性促进不对称整合素富集，表明α PS 3/βPS运输以极化方式发生。我们发现，以前已知的几个基因在贩运和细胞迁移中的作用也需要吞噬。此外，与哺乳动物一样，果蝇中的专职和非专职吞噬细胞和迁移细胞也需要相同的α-整联蛋白亚基。我们的研究结果表明，迁移和吞噬细胞使用共同的机制，并证明了整合素功能和极化的整合素亚基在吞噬过程中的贩运的关键作用。这项研究还建立了果蝇卵巢上皮滤泡细胞作为一个强大的模型，了解所需的分子变化的吞噬极化上皮。总结：顶端整合素定位，介导的极化和定向运输，是至关重要的上皮细胞的适当吞噬。
Inefficient clearance of dead cells or debris by epithelial cells can lead to or exacerbate debilitating conditions such as retinitis pigmentosa, macular degeneration, chronic obstructive pulmonary disease and asthma. Despite the importance of engulfment by epithelial cells, little is known about the molecular changes that are required within these cells. The misregulation of integrins has previously been associated with disease states, suggesting that a better understanding of the regulation of receptor trafficking could be key to treating diseases caused by defects in phagocytosis. Here, we demonstrate that the integrin heterodimer αPS3/βPS becomes apically enriched and is required for engulfment by the epithelial follicle cells of the Drosophila ovary. We found that integrin heterodimer localization and function is largely directed by the α-subunit. Moreover, proper cell polarity promotes asymmetric integrin enrichment, suggesting that αPS3/βPS trafficking occurs in a polarized fashion. We show that several genes previously known for their roles in trafficking and cell migration are also required for engulfment. Moreover, as in mammals, the same α-integrin subunit is required by professional and non-professional phagocytes and migrating cells in Drosophila. Our findings suggest that migrating and engulfing cells use common machinery, and demonstrate a crucial role for integrin function and polarized trafficking of integrin subunits during engulfment. This study also establishes the epithelial follicle cells of the Drosophila ovary as a powerful model for understanding the molecular changes required for engulfment by a polarized epithelium. Summary: Apical integrin localization, mediated by polarized and directed trafficking, is crucial for proper engulfment by epithelial cells.