Sahu Aresh, Ghosh Ritabrata, Deshpande Girish, Prasad Mohit
Department of Biological Sciences Indian Institute of Science Education & Research Kolkata Mohanpur Campus Mohanpur, Nadia, West Bengal, India.
Department of Molecular Biology Princeton University, Princeton, NJ, United States of America.
PLoS Genet. 2017 Jan 23;13(1):e1006542. doi: 10.1371/journal.pgen.1006542. eCollection 2017 Jan.
Intercellular communication mediated by gap junction (GJ) proteins is indispensable during embryogenesis, tissue regeneration and wound healing. Here we report functional analysis of a gap junction protein, Innexin 2 (Inx2), in cell type specification during Drosophila oogenesis. Our data reveal a novel involvement of Inx2 in the specification of Border Cells (BCs), a migratory cell type, whose identity is determined by the cell autonomous STAT activity. We show that Inx2 influences BC fate specification by modulating STAT activity via Domeless receptor endocytosis. Furthermore, detailed experimental analysis has uncovered that Inx2 also regulates a calcium flux that transmits across the follicle cells. We propose that Inx2 mediated calcium flux in the follicle cells stimulates endocytosis by altering Dynamin (Shibire) distribution which is in turn critical for careful calibration of STAT activation and, thus for BC specification. Together our data provide unprecedented molecular insights into how gap junction proteins can regulate cell-type specification.
由间隙连接（GJ）蛋白介导的细胞间通讯在胚胎发育、组织再生和伤口愈合过程中不可或缺。在此，我们报告了间隙连接蛋白Innexin 2（Inx2）在果蝇卵子发生过程中细胞类型特化方面的功能分析。我们的数据揭示了Inx2在边界细胞（BCs）特化中的新作用，BCs是一种迁移性细胞类型，其身份由细胞自主的STAT活性决定。我们表明，Inx2通过无受体胞吞作用调节STAT活性，从而影响BC命运特化。此外，详细的实验分析发现，Inx2还调节跨卵泡细胞的钙通量。我们提出，卵泡细胞中Inx2介导的钙通量通过改变发动蛋白（Shibire）的分布来刺激胞吞作用，这反过来对于精确校准STAT激活至关重要，因此对于BC特化也至关重要。我们的数据共同为间隙连接蛋白如何调节细胞类型特化提供了前所未有的分子见解。
