Devergne Olivier, Sun Gina H, Schüpbach Trudi
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Cell Rep. 2017 Feb 21;18(8):1831-1839. doi: 10.1016/j.celrep.2017.02.002.
The basement membrane (BM), a sheet of extracellular matrix lining the basal side of epithelia, is essential for epithelial cell function and integrity, yet the mechanisms that control the basal restriction of BM proteins are poorly understood. In epithelial cells, a specialized pathway is dedicated to restrict the deposition of BM proteins basally. Here, we report the identification of a factor in this pathway, a homolog of the mammalian guanine nucleotide exchange factor (GEF) Mss4, which we have named Stratum. The loss of Stratum leads to the missecretion of BM proteins at the apical side of the cells, forming aberrant layers in close contact with the plasma membrane. We found that Rab8GTPase acts downstream of Stratum in this process. Altogether, our results uncover the importance of this GEF/Rab complex in specifically coordinating the basal restriction of BM proteins, a critical process for the establishment and maintenance of epithelial cell polarity.
基底膜(BM)是一层位于上皮细胞基底侧的细胞外基质,对上皮细胞的功能和完整性至关重要,然而,控制BM蛋白基底限制的机制却知之甚少。在上皮细胞中,有一条专门的途径用于限制BM蛋白在基底侧的沉积。在此,我们报告了该途径中一个因子的鉴定,它是哺乳动物鸟嘌呤核苷酸交换因子(GEF)Mss4的同源物,我们将其命名为Stratum。Stratum的缺失导致BM蛋白在细胞顶端侧错误分泌,形成与质膜紧密接触的异常层。我们发现Rab8 GTP酶在此过程中作用于Stratum的下游。总之,我们的结果揭示了这种GEF/Rab复合物在特异性协调BM蛋白基底限制方面的重要性,这是上皮细胞极性建立和维持的关键过程。