title: SNX18 shares a redundant role with SNX9 and modulates endocytic trafficking at the plasma membrane.
abstract: SNX18 and SNX9 are members of a subfamily of SNX (sorting nexin) proteins with the same domain structure. Although a recent report showed that SNX18 and SNX9 localize differently in cells and appear to function in different trafficking pathways, concrete evidence regarding whether they act together or separately in intracellular trafficking is still lacking. Here, we show that SNX18 has a similar role to SNX9 in endocytic trafficking at the plasma membrane, rather than having a distinct role. SNX18 and SNX9 are expressed together in most cell lines, but to a different extent. Like SNX9, SNX18 interacts with dynamin and stimulates the basal GTPase activity of dynamin. It also interacts with neuronal Wiskott-Aldrich syndrome protein (N-WASP) and synaptojanin, as does SNX9. SNX18 and SNX9 can form a heterodimer and colocalize in tubular membrane structures. Depletion of SNX18 by small hairpin RNA inhibited transferrin uptake. SNX18 successfully compensates for SNX9 deficiency during clathrin-mediated endocytosis and vice versa. Total internal reflection fluorescence microscopy in living cells shows that a transient burst of SNX18 recruitment to clathrin-coated pits coincides spatiotemporally with a burst of dynamin and SNX9. Taken together, our results suggest that SNX18 functions with SNX9 in multiple pathways of endocytosis at the plasma membrane and that they are functionally redundant.
authors.affiliation: Department of Biomedical Sciences, Seoul National University, College of Medicine, Seoul 110-799, South Korea.
authors.forename: Joohyun
authors.initials: J
authors.lastname: Park
authors.forename: Yoonju
authors.initials: Y
authors.lastname: Kim
authors.forename: Suho
authors.initials: S
authors.lastname: Lee
authors.forename: Jae Jun
authors.initials: JJ
authors.lastname: Park
authors.forename: Zee Yong
authors.initials: ZY
authors.lastname: Park
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.forename: Sunghoe
authors.initials: S
authors.lastname: Chang
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism*; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C530791:SNX18 protein, human; C400533:SNX9 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases; D034281:Dynamins