SLIC-1/sorting nexin 20: a novel sorting nexin that directs subcellular distribution of PSGL-1.
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.
Schaff
Ulrich Y
UY
Department of Biomedical Engineering, University of California Davis, Davis, CA 95616, USA.
Shih
Heather H
HH
Lorenz
Meike
M
Sako
Dianne
D
Kriz
Ron
R
Milarski
Kim
K
Bates
Brian
B
Tchernychev
Boris
B
Shaw
Gray D
GD
Simon
Scott I
SI
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D019556:COS Cells; D002352:Carrier Proteins / Q000302:isolation & purification / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D019007:P-Selectin / Q000378:metabolism*; D058305:Sorting Nexins / Q000302:isolation & purification / Q000502:physiology*; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000302:isolation & purification / Q000502:physiology*
D002352:Carrier Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; C528103:SNX20 protein, human; C000600447:SNX20 protein, mouse; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins