SLIC-1/sorting nexin 20: A novel sorting nexin that directs subcellular distribution of PSGL-1

Ulrich Y. Schaff, Heather H. Shih, Meike Lorenz, Dianne Sako, Ron Kris, Kim Milarski, Brian Bates, Boris Tchernychev, Gray D. Shaw, Scott I. Simon

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

P-Selectin glycoprotein ligand-1 (PSGL-1) is a mucin-like glycoprotein expressed on the surface of leukocytes that serves as the major ligand for the selectin family of adhesion molecules and functions in leukocyte tethering and rolling on activated endothelium and platelets. Previous studies have implicated the highly conserved cytoplasmic domain of PSGL-1 in regulating outside-in signaling of integrin activation. However, molecules that physically and functionally interact with this domain are not completely defined. Using a yeast two-hybrid screen with the cytoplasmic domain of PSGL-1 as bait, a novel protein designated selectin ligand interactor cytoplasmic-1 (SLIC-1) was isolated. Computer-based homology search revealed that SLIC-1 was the human orthologue for the previously identified mouse sorting nexin 20. Direct interaction between SLIC-1 and PSGL-1 was specific as indicated by co-immunoprecipitation and motif mapping. Colocalization experiments demonstrated that SLIC-1 contains a Phox homology domain that binds phosphoinositides and targets the PSGL-1/SLIC-1 complex to endosomes. Deficiency in the murine homologue of SLIC-1 did not modulate PSGL-1-dependent signaling nor alter neutrophil adhesion through PSGL-1. We conclude that SLIC-1 serves as a sorting molecule that cycles PSGL-1 into endosomes with no impact on leukocyte recruitment.

Original languageEnglish (US)
Pages (from-to)550-564
Number of pages15
JournalEuropean Journal of Immunology
Volume38
Issue number2
DOIs
StatePublished - Feb 2008

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Keywords

  • Cell surface molecules
  • Leukocytes
  • Protein trafficking
  • Selectins

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Schaff, U. Y., Shih, H. H., Lorenz, M., Sako, D., Kris, R., Milarski, K., Bates, B., Tchernychev, B., Shaw, G. D., & Simon, S. I. (2008). SLIC-1/sorting nexin 20: A novel sorting nexin that directs subcellular distribution of PSGL-1. European Journal of Immunology, 38(2), 550-564. https://doi.org/10.1002/eji.200737777