Ungewickell Alexander, Ward Michael E, Ungewickell Ernst, Majerus Philip W
Division of Hematology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13501-6. doi: 10.1073/pnas.0405664101. Epub 2004 Sep 7.
The subcellular localization of Ocrl, the inositol polyphosphate 5-phosphatase that is mutated in Lowe syndrome, was investigated by fluorescence microscopy. Ocrl was localized to endosomes and Golgi membranes along with clathrin, giantin, the mannose 6-phosphate receptor, transferrin, and the early endosomal antigen 1 endosomal marker in fixed cells. The endosomal localization of Ocrl was confirmed by live-cell time-lapse microscopy in which we monitored the dynamics of Ocrl on endosomes. GST binding assays show that Ocrl interacts with the clathrin terminal domain and the clathrin adaptor protein AP-2. Our findings suggest a role for Ocrl in endosomal receptor trafficking and sorting.
通过荧光显微镜研究了在劳氏综合征中发生突变的肌醇多磷酸5-磷酸酶Ocrl的亚细胞定位。在固定细胞中,Ocrl与网格蛋白、巨蛋白、甘露糖6-磷酸受体、转铁蛋白以及早期内体抗原1内体标记物一起定位于内体和高尔基体膜。通过活细胞延时显微镜观察Ocrl在内体上的动态变化,证实了Ocrl在内体中的定位。谷胱甘肽S-转移酶(GST)结合试验表明,Ocrl与网格蛋白末端结构域和网格蛋白衔接蛋白AP-2相互作用。我们的研究结果表明Ocrl在内体受体运输和分选过程中发挥作用。