Dansereau David A, Lasko Paul
Department of Biology, McGill University, Montreal, Quebec, Canada.
J Cell Biol. 2008 Sep 8;182(5):963-77. doi: 10.1083/jcb.200711046. Epub 2008 Sep 1.
Experiments in cultured cells with Ran-binding protein M (RanBPM) suggest that it links cell surface receptors and cell adhesion proteins. In this study, we undertake a genetic study of RanBPM function in the germline stem cell (GSC) niche of Drosophila melanogaster ovaries. We find that two RanBPM isoforms are produced from alternatively spliced transcripts, the longer of which is specifically enriched in the GSC niche, a cluster of somatic cells that physically anchors GSCs and expresses signals that maintain GSC fate. Loss of the long isoform from the niche causes defects in niche organization and cell size and increases the number of GSCs attached to the niche. In genetic mosaics for a null RanBPM allele, we find a strong bias for GSC attachment to mutant cap cells and observe abnormal accumulation of the adherens junction component Armadillo (beta-catenin) and the membrane skeletal protein Hu-li tai shao in mutant terminal filament cells. These results implicate RanBPM in the regulation of niche capacity and adhesion.
对培养细胞中与Ran结合蛋白M(RanBPM)进行的实验表明,它将细胞表面受体与细胞粘附蛋白联系起来。在本研究中,我们对RanBPM在黑腹果蝇卵巢生殖系干细胞(GSC)微环境中的功能进行了遗传学研究。我们发现,两种RanBPM异构体由选择性剪接的转录本产生,其中较长的异构体在GSC微环境中特异性富集,GSC微环境是一群体细胞,它物理上锚定GSCs并表达维持GSC命运的信号。微环境中长异构体的缺失会导致微环境组织和细胞大小出现缺陷,并增加附着在微环境上的GSCs数量。在RanBPM无效等位基因的遗传嵌合体中,我们发现GSC附着于突变帽细胞存在强烈偏向性,并观察到突变终丝细胞中粘附连接成分犰狳(β-连环蛋白)和膜骨架蛋白“糊涂太少”(Hu-li tai shao)异常积累。这些结果表明RanBPM参与微环境容量和粘附的调节。