Adaptor protein sorting nexin 17 interacts with the scavenger receptor FEEL-1/stabilin-1 and modulates its expression on the cell surface.
The scavenger receptor FEEL-1/stabilin-1 is known as the marker of alternatively activated macrophage and sinusoidal endothelial cell. FEEL-1/stabilin-1 is a multifunctional transmembrane glycoprotein that is implicated in bacterial infection, diabetes, atherosclerosis, wound healing, and innate immunity. In the current study, we have identified the phox-homology domain containing protein SNX17 as a novel interaction partner of FEEL-1/stabilin-1 in endothelial cells. SNX17 directly interacts with FEEL-1/stabilin-1 and regulates its trafficking. Studies using the cytoplasmic domain of truncated or mutant FEEL-1/stabilin-1 suggest that the NPxF motif of the FEEL-1/stabilin-1 cytoplasmic tail is required for its interaction with SNX17. By transfecting cells with small interfering RNA targeting SNX17, total cellular FEEL-1/stabilin-1 expression and FEEL-1/stabilin-1-mediated ligand uptake were significantly decreased due to the enhancement of FEEL-1/stabilin-1 protein degradation. Our results identify SNX17 as a novel interaction partner of FEEL-1/stabilin-1 in endothelial cells.
Adachi
Hideki
H
Laboratory of Cellular Biochemistry, RIKEN, Saitama 351-0198, Japan. adachih@riken.jp
Tsujimoto
Masafumi
M
D000595:Amino Acid Sequence; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D058305:Sorting Nexins; D020798:Two-Hybrid System Techniques; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D034741:RNA, Small Interfering; D016201:Receptors, Lymphocyte Homing; C487895:SNX17 protein, human; C449926:STAB1 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins