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Originally published as MBC in Press, 10.1091/mbc.E04-02-0143 on April 30, 2004

Vol. 15, Issue 7, 3095-3105, July 2004

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Sorting Nexin 17 Accelerates Internalization Yet Retards Degradation of P-selectin

Ross Williams * {dagger}, Thomas Schlüter {dagger} {ddagger}, Marnie S. Roberts * {dagger}, Peter Knauth {ddagger}, Ralf Bohnensack {ddagger}, and Daniel F. Cutler * §

* MRC Laboratory for Molecular Cell Biology, Cell Biology Unit and Department of Biochemistry and Molecular Biology, University College London, London, United Kingdom; {ddagger} Institute for Biochemistry, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany

Submitted February 23, 2004; Revised April 6, 2004; Accepted April 7, 2004
Monitoring Editor: Juan S. Bonifacino

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.


Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E04-02-0143. Article and publication date are available at www.molbiolcell.org/cgi/doi/10.1091/mbc.E04-02-0143.

{dagger} These authors contributed equally to this work.

§ Corresponding author. E-mail address: d.cutler{at}ucl.ac.uk.Abbreviations used: AK6, anti-P-selectin antibody; EEA1, early endosome antigene; FERM, four.1 protein, ezrin, radixin, moesin; LAMP-1, lysosome-associated membrane protein; LBPA, lyso-bisphosphatidic acid; LDL, low-density lipoprotein; M6PR, mannose-6-phosphate receptor; PI(3)P, phosphatidylinositol 3-phosphate; PX, phox homology; SNX, sorting nexin; TfnR, transferrin receptor; WPB, Weibel Palade body




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J. Lee, C. Retamal, L. Cuitino, A. Caruano-Yzermans, J.-E. Shin, P. van Kerkhof, M.-P. Marzolo, and G. Bu
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