Sorting nexin 17 accelerates internalization yet retards degradation of P-selectin.
The transient appearance of P-selectin on the surface of endothelial cells helps recruit leukocytes into sites of inflammation. The tight control of cell surface P-selectin on these cells depends on regulated exocytosis of Weibel-Palade bodies where the protein is stored and on its rapid endocytosis. After endocytosis, P-selectin is either sorted via endosomes and the Golgi apparatus for storage in Weibel-Palade bodies or targeted to lysosomes for degradation. A potential player in this complex endocytic itinerary is SNX17, a member of the sorting nexin family, which has been shown in a yeast two-hybrid assay to bind P-selectin. Here, we show that overexpression of SNX17 in mammalian cells can influence two key steps in the endocytic trafficking of P-selectin. First, it promotes the endocytosis of P-selectin from the plasma membrane. Second, it inhibits the movement of P-selectin into lysosomes, thereby reducing its degradation.
Williams
Ross
R
MRC Laboratory for Molecular Cell Biology, Cell Biology Unit and Department of Biochemistry and Molecular Biology, University College London, London, United Kingdom.
Schlüter
Thomas
T
Roberts
Marnie S
MS
Knauth
Peter
P
Bohnensack
Ralf
R
Cutler
Daniel F
DF
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000276:immunology / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008247:Lysosomes / Q000502:physiology; D019007:P-Selectin / Q000032:analysis / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000502:physiology; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D002352:Carrier Proteins; D019007:P-Selectin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D000077191:Wortmannin; C487895:SNX17 protein, human