title: Evidence for a role of SNX16 in regulating traffic between the early and later endosomal compartments.
abstract: 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.
authors.affiliation: Membrane Biology Laboratory, Institute of Molecular and Cell Biology, Singapore 117609, Singapore.
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Hanson
authors.forename: Wanjin
authors.initials: W
authors.lastname: Hong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology*; D002499:Centrifugation, Density Gradient; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D058305:Sorting Nexins; D013395:Sucrose / Q000494:pharmacology; D014018:Tissue Distribution; D014162:Transfection; D014407:Tumor Cells, Cultured; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C477748:SNX16 protein, human; C477749:Snx16 protein, mouse; C477750:Snx16 protein, rat; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D013395:Sucrose; D004815:Epidermal Growth Factor; D005982:Glutathione Transferase