The nuclear architectural protein HMGA1a triggers receptor-mediated endocytosis.
The nuclear architectural protein HMGA1a triggers receptor-mediated endocytosis.
复制标题
核结构蛋白 HMGA1a 触发受体介导的内吞作用。
DOI：
10.1002/jcb.22281
复制
发表时间：
2009
影响因子：
4
通讯作者：
Li,AlexanderDQ
中科院分区：
文献类型：
--
作者：
Wu,Wuwei;Wan,Wei;Li,AlexanderDQ
高迁移率族蛋白 A (HMGA) 是核结构因子，位于细胞核中，主要执行基因调节功能。然而，我们的结果表明，HMGA 成员 (HMGA1a) 具有独特的质膜受体；该受体特异性结合 HMGA 修饰的物质，有效介导内吞作用，并将细胞外 HMGA 功能化的货物内化。事实上，用 HMGA1a 蛋白标记的染料或纳米颗粒很容易进入 Hela 细胞。使用 stratagem 化学交联剂，我们将 HMGA 受体与 HMGA1a-GFP 融合蛋白共价结合，从而捕获质膜受体。随后的蛋白质印迹和 SDS-PAGE 凝胶显示 HMGA 受体是一种 26-kDa 蛋白质。共聚焦活细胞显微成像用于监测整个内吞过程，其中内化的 HMGA1a 修饰物质由微管上的运动蛋白运输，并最终到达晚期内体/溶酶体。细胞活力测定还表明，细胞外 HMGA1a 蛋白以剂量依赖性方式直接影响 Hela 细胞的生存能力，这意味着 HMGA1a 蛋白的多功能性及其抑制癌细胞生存和调节生长的有效作用。 J.细胞。生物化学。 108: 791–801, 2009。© 2009 Wiley-Liss, Inc.
High mobility group proteins A (HMGA), nuclear architectural factors, locate in the cell nuclei and mostly execute gene‐regulation function. However, our results reveal that a HMGA member (HMGA1a) has a unique plasma membrane receptor; this receptor specifically binds to HMGA‐decorated species, effectively mediates endocytosis, and internalizes extracellular HMGA‐functionalized cargoes. Indeed, dyes or nanoparticles labeled with HMGA1a protein readily enter Hela cells. Using a stratagem chemical cross‐linker, we covalently bonded the HMGA receptor to the HMGA1a‐GFP fusion protein, thus capturing the plasma membrane receptor. Subsequent Western blots and SDS–PAGE gel revealed that the HMGA receptor is a 26‐kDa protein. Confocal live‐cell microscopic imaging was used to monitor the whole endocytic process, in which the internalized HMGA1a‐decorated species are transported by motor proteins on microtubules and eventually arrive at the late endosomes/lysosomes. Cell viability assays also suggested that extracellular HMGA1a protein directly influences the survival ability of Hela cells in a dose‐dependent manner, implying versatility of HMGA1a protein and its potent role to suppress cancer cell survivability and to regulate growth. J. Cell. Biochem. 108: 791–801, 2009. © 2009 Wiley‐Liss, Inc.