National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, 685-1 Yangcheong-ri, Ochang-eup, Chung-buk 363-883, Republic of Korea.
Biochem Biophys Res Commun. 2010 Dec 10;403(2):167-71. doi: 10.1016/j.bbrc.2010.10.121. Epub 2010 Oct 30.
The retromer complex, which mediates retrograde transport from endosomes to the trans-Golgi network, is a heteropentameric complex that contains a multifunctional cargo recognition heterotrimer consisted of the vacuolar protein sorting (Vps) subunits Vps26, Vps29, and Vps35. In mammals, there are two different isoforms of Vps26, Vps26a and Vps26b, that localize to the endosome, and to the plasma membrane, respectively. To elucidate the biological significance of the Vps26b isoform, we generated Vps26b knockout mice and studied their molecular, histological, and behavioral phenotypes. We found that the loss of Vps26b results in no significant defects in the behavior, body size, and health of the mice. Vps26b-deficient mice showed a severe reduction of Vps35 protein at cellular level and lacked the Vps26b-Vps29-Vps35 retromer complex, despite the normal presence of the Vps26a-Vps29-Vps35 retromer complex. Relatively, the amount of sortilin was increased approximately 20% in the Vps26b-deficient mice, whereas the sorLA was normal. These results suggest that mouse Vps26b-Vps29-Vps35 retromer complex is implicated in the transport of sortilin from endosomes to the trans-Golgi network (TGN).
返回体复合物介导了从内体到反式高尔基体网络的逆行运输，是一种异五聚体复合物，包含一个多功能货物识别异三聚体，由液泡蛋白分选（Vps）亚基 Vps26、Vps29 和 Vps35 组成。在哺乳动物中，有两种不同的 Vps26 同工型，Vps26a 和 Vps26b，分别定位于内体和质膜。为了阐明 Vps26b 同工型的生物学意义，我们生成了 Vps26b 敲除小鼠，并研究了它们的分子、组织学和行为表型。我们发现，Vps26b 的缺失不会导致小鼠行为、体型和健康出现显著缺陷。Vps26b 缺陷型小鼠在细胞水平上表现出 Vps35 蛋白的严重减少，并且缺乏 Vps26b-Vps29-Vps35 逆行体复合物，尽管存在正常的 Vps26a-Vps29-Vps35 逆行体复合物。相对地，Vps26b 缺陷型小鼠中的 sortilin 量增加了约 20%，而 sorLA 则正常。这些结果表明，小鼠 Vps26b-Vps29-Vps35 逆行体复合物参与了 sortilin 从内体到反式高尔基体网络（TGN）的运输。
