PDF(Pubmed)
Abstract：
The SLC35 (Solute Carrier 35) family members acting as nucleotide sugar transporters are typically localized in the endoplasmic reticulum or Golgi apparatus. It is, therefore, intriguing that some reports document the presence of orphan transporters SLC35F1 and SLC35F6 within the endosomal and lysosomal system. Here, we compared the subcellular distribution of these proteins and found that they are concentrated in separate compartments; i.e., recycling endosomes for SLC35F1 and lysosomes for SLC35F6. Swapping the C-terminal tail of these proteins resulted in a switch of localization, with SLC35F1 being trafficked to lysosomes while SLC35F6 remained in endosomes. This suggested the presence of specific sorting signals in these C-terminal regions. Using site-directed mutagenesis, fluorescence microscopy, and cell surface biotinylation assays, we found that the EQERLL360 signal located in the cytoplasmic tail of human SLC35F6 is involved in its lysosomal sorting (as previously shown for this conserved sequence in mouse SLC35F6), and that SLC35F1 localization in the recycling pathway depends on two YXXΦ-type signals: a Y367KQF sequence facilitates its internalization from the plasma membrane, while a Y392TSL motif prevents its transport to lysosomes, likely by promoting SLC35F1 recycling to the cell surface. Taken together, these results support that some SLC35 members may function at different levels of the endosomal and lysosomal system.
摘要：
充当核苷酸糖转运蛋白的SLC35(溶质载体35)家族成员通常位于内质网或高尔基体中。是的,因此,有趣的是，一些报告记录在内体和溶酶体系统中存在孤儿转运蛋白SLC35F1和SLC35F6。这里,我们比较了这些蛋白质的亚细胞分布，发现它们集中在不同的区室中；即，SLC35F1的循环内体和SLC35F6的溶酶体。交换这些蛋白质的C末端尾部导致定位的转换，SLC35F1被运输到溶酶体，而SLC35F6保留在内体中。这表明在这些C末端区域中存在特定的分选信号。使用定点诱变，荧光显微镜,和细胞表面生物素化分析，我们发现位于人SLC35F6细胞质尾的EQERLL360信号参与其溶酶体分选（如先前在小鼠SLC35F6中显示的该保守序列），并且SLC35F1在再循环途径中的定位取决于两个YXXΦ型信号：Y367KQF序列促进其从质膜的内化，虽然Y392TSL基序阻止其运输到溶酶体，可能通过促进SLC35F1循环到细胞表面。一起来看,这些结果支持一些SLC35成员可能在内体和溶酶体系统的不同水平上发挥作用.
