Zhou Guo Ling, Na Soon-Young, Niedra Rasma, Seed Brian
Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA
Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
J Cell Sci. 2014 Sep 15;127(Pt 18):3916-27. doi: 10.1242/jcs.135269. Epub 2014 May 20.
GPR107 is a type III integral membrane protein that was initially predicted to be a member of the family of G-protein-coupled receptors. This report shows that deletion of Gpr107 leads to an embryonic lethal phenotype that is characterized by a reduction in cubilin transcript abundance and a decrease in the representation of multiple genes implicated in the cubilin-megalin endocytic receptor complex (megalin is also known as LRP2). Gpr107-null fibroblast cells exhibit reduced transferrin internalization, decreased uptake of low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) cargo and resistance to toxins. Colocalization studies and proteomic analyses suggest that GPR107 associates with clathrin and the retromer protein VPS35 and that GPR107 might be responsible for the return of receptors to the plasma membrane from endocytic compartments. The highly selective deficits observed in Gpr107-null cells indicate that GPR107 interacts directly or indirectly with a limited subset of surface receptors.
GPR107是一种III型整合膜蛋白，最初被预测为G蛋白偶联受体家族的成员。本报告显示，Gpr107的缺失导致胚胎致死表型，其特征是cubilin转录本丰度降低以及与cubilin-巨蛋白内吞受体复合物（巨蛋白也称为LRP2）相关的多个基因的表达减少。Gpr107基因敲除的成纤维细胞表现出转铁蛋白内化减少、低密度脂蛋白（LDL）受体相关蛋白-1（LRP1）货物摄取减少以及对毒素的抗性。共定位研究和蛋白质组学分析表明，GPR107与网格蛋白和逆向转运蛋白VPS35相关联，并且GPR107可能负责将受体从内吞小室返回到质膜。在Gpr107基因敲除细胞中观察到的高度选择性缺陷表明，GPR107直接或间接与有限的表面受体亚群相互作用。
