Rapaport Debora, Auerbach Wojtek, Naslavsky Naava, Pasmanik-Chor Metsada, Galperin Emilia, Fein Amos, Caplan Steve, Joyner Alexandra L, Horowitz Mia
Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
Traffic. 2006 Jan;7(1):52-60. doi: 10.1111/j.1600-0854.2005.00359.x.
EHD1 is a member of the EHD family that contains four mammalian homologs. Among the invertebrate orthologs are a single Drosophila and Caenorhabditis elegans proteins and two plant members. They all contain three modules, a N-terminal domain that contains nucleotide-binding motifs, a central coiled-coil domain involved in oligomerization and a C-terminal region that harbors the EH domain. Studies in C. elegans and EHD1 depletion by RNA interference in human cells have demonstrated that it regulates recycling of membrane proteins. We addressed the physiological role of EHD1 through its inactivation in the mouse. Ehd1 knockout mice were indistinguishable from normal mice, had a normal life span and showed no histological abnormalities. Analysis of transferrin uptake in Ehd1(-/-) embryonic fibroblasts demonstrated delayed recycling to the plasma membrane with accumulation of transferrin in the endocytic recycling compartment. Our results corroborate the established role of EHD1 in the exit of membrane proteins from recycling endosomes in vivo in a mouse model.
EHD1是EHD家族的成员之一，该家族包含四个哺乳动物同源物。在无脊椎动物直系同源物中，有单个果蝇和秀丽隐杆线虫蛋白以及两个植物成员。它们都包含三个模块，一个含有核苷酸结合基序的N端结构域、一个参与寡聚化的中央卷曲螺旋结构域和一个含有EH结构域的C端区域。秀丽隐杆线虫的研究以及在人类细胞中通过RNA干扰使EHD1缺失的研究表明，它调节膜蛋白的循环利用。我们通过在小鼠体内使其失活来探究EHD1的生理作用。Ehd1基因敲除小鼠与正常小鼠无异，寿命正常，且未表现出组织学异常。对Ehd1(-/-)胚胎成纤维细胞中转铁蛋白摄取的分析表明，转铁蛋白向质膜的循环延迟，在内吞循环区室中积累。我们的结果证实了EHD1在小鼠模型体内从循环内体中输出膜蛋白方面已确定的作用。
