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Recycling to the Plasma Membrane is Delayed in EHD1 Knockout Mice

机译:EHD1基因敲除小鼠延迟到血浆膜的回收。

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摘要

EHD1 is a member of the EHD family that contains four mammalian homologs. Among the invertebrate ortho-logs 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 fibro-blasts demonstrated delayed recycling to the plasma membrane with accumulation of transferrin in the endo-cytic 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.
机译:EHD1是EHD家族的成员,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,有一个果蝇和秀丽隐杆线虫蛋白质以及两个植物成员。它们都包含三个模块,一个包含核苷酸结合基序的N末端结构域,一个参与寡聚化的中央卷曲螺旋结构域,另一个包含EH结构域的C末端区域。在人体细胞中通过RNA干扰对秀丽隐杆线虫和EHD1进行的研究表明,它调节膜蛋白的回收。我们通过在小鼠中使其失活来解决EHD1的生理作用。 Ehd1基因敲除小鼠与正常小鼠没有区别,寿命正常,没有组织学异常。对Ehd1〜(-/-)胚胎成纤维细胞中转铁蛋白摄取的分析表明,由于内吞循环室中的转铁蛋白积累,延迟了质膜的循环。我们的研究结果证实了EHD1在小鼠模型中体内循环体内的膜蛋白退出中已确立的作用。

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