Hanson Brendon J, Hong Wanjin
Membrane Biology Laboratory, Institute of Molecular and Cell Biology, Singapore 117609, Singapore.
J Biol Chem. 2003 Sep 5;278(36):34617-30. doi: 10.1074/jbc.M300143200. Epub 2003 Jun 17.
Sorting nexins (SNXs) are a growing family of proteins characterized by the presence of a PX domain. The PX domain mediates membrane association by interaction with phosphoinositides. The SNXs are generally believed to participate in membrane trafficking, but information regarding the function of individual proteins is limited. In this report, we describe the major characteristics of one member, SNX16. SNX16 is a novel 343-amino acid protein consisting of a central PX domain followed by a potential coiled-coil domain and a C-terminal region. Like other sorting nexins, SNX16 associates with the membrane via the PX domain which interacts with the phospholipid phosphatidylinositol 3-phosphate. We show via biochemical and cellular studies that SNX16 is distributed in both early and late endosome/lysosome structures. The coiled-coil domain is necessary for localization to the later endosomal structures, as mutant SNX16 lacking this domain was found only in early endosomes. Trafficking of internalized epidermal growth factor was also delayed by this SNX16 mutant, as these cells showed a delay in the segregation of epidermal growth factor in the early endosome for its delivery to later compartments. In addition, the coiled-coil domain is shown here to be important for homo-oligomerization of SNX16. Taken together, these results suggest that SNX16 is a sorting nexin that may function in the trafficking of proteins between the early and late endosomal compartments.
分选连接蛋白(SNXs)是一个不断扩大的蛋白质家族,其特征是存在一个PX结构域。PX结构域通过与磷酸肌醇相互作用介导与膜的结合。一般认为SNXs参与膜运输,但关于单个蛋白质功能的信息有限。在本报告中,我们描述了一个成员SNX16的主要特征。SNX16是一种新的343个氨基酸的蛋白质,由一个中央PX结构域、一个潜在的卷曲螺旋结构域和一个C末端区域组成。与其他分选连接蛋白一样,SNX16通过与磷脂酰肌醇3-磷酸相互作用的PX结构域与膜结合。我们通过生化和细胞研究表明,SNX16分布在早期和晚期内体/溶酶体结构中。卷曲螺旋结构域是定位于晚期内体结构所必需的,因为缺乏该结构域的突变型SNX16仅在早期内体中发现。内化的表皮生长因子的运输也被这种SNX16突变体延迟,因为这些细胞在早期内体中表皮生长因子向晚期区室的递送中显示出分离延迟。此外,这里显示卷曲螺旋结构域对SNX16的同源寡聚化很重要。综上所述,这些结果表明SNX16是一种分选连接蛋白,可能在早期和晚期内体区室之间的蛋白质运输中发挥作用。