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MBC in Press, published online ahead of print April 30, 2004
Mol. Biol. Cell 10.1091/mbc.E04-02-0143

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Submitted on February 23, 2004
Revised on April 6, 2004
Accepted on April 7, 2004

Sorting nexin 17 accelerates internalisation yet retards degradation of P-selectin

Ross Williams1, Thomas Schlüter2, Marnie S. Roberts1, Peter Knauth2, Ralf Bohnensack2, and Daniel F. Cutler3*

1 MRC Laboratory for Molecular Cell Biology, Cell Biology Unit and Department of Biochemistry and Molecular Biology, University College London, London, UK
2 Institute for Biochemistry, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany
3 MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, UCL, Gower St., London WC1E 6BT

* Corresponding author. E-mail address: d.cutler{at}ucl.ac.uk.

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. Following 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.




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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
Adaptor Protein Sorting Nexin 17 Regulates Amyloid Precursor Protein Trafficking and Processing in the Early Endosomes
J. Biol. Chem., April 25, 2008; 283(17): 11501 - 11508.
[Abstract] [Full Text] [PDF]




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