Implication of mouse Vps26b-Vps29-Vps35 retromer complex in sortilin trafficking
Implication of mouse Vps26b-Vps29-Vps35 retromer complex in sortilin trafficking
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DOI：
10.1016/j.bbrc.2010.10.121
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发表时间：
2010-12-10
影响因子：
3.1
通讯作者：
Chang, Kyu-Tae
中科院分区：
文献类型：
--
作者：
Kim, Ekyune;Lee, Youngjeon;Chang, Kyu-Tae
逆转录复合物介导从内体到跨高尔基体网络的逆行转运，是一种异五聚体复合物，包含多功能货物识别异三聚体，该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，Vps26 有两种不同的亚型：Vps26a 和 Vps26b，分别定位于内体和质膜。为了阐明 Vps26b 亚型的生物学意义，我们培育了 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的行为、体型和健康出现明显缺陷。 Vps26b缺陷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逆转录酶复合物，尽管Vps26a-Vps29-Vps35逆转录酶复合物正常存在。相对而言，Vps26b 缺陷小鼠的 sortilin 量增加了约 20%，而 sorLA 则正常。这些结果表明，小鼠 Vps26b-Vps29-Vps35 逆转录体复合物参与分拣蛋白从内体到跨高尔基体网络 (TGN) 的转运。 (C) 2010 Elsevier Inc. 保留所有权利。
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). (C) 2010 Elsevier Inc. All rights reserved.