Back to Search
Start Over
Separable requirements for cytoplasmic domain of PSGL-1 in leukocyte rolling and signaling under flow.
- Source :
-
Blood [Blood] 2008 Sep 01; Vol. 112 (5), pp. 2035-45. Date of Electronic Publication: 2008 Jun 11. - Publication Year :
- 2008
-
Abstract
- In inflamed venules, leukocytes use P-selectin glycoprotein ligand-1 (PSGL-1) to roll on P-selectin and E-selectin and to activate integrin alphaLbeta2 (lymphocyte function-associated antigen-1, LFA-1) to slow rolling on intercellular adhesion molecule-1 (ICAM-1). Studies in cell lines have suggested that PSGL-1 requires its cytoplasmic domain to localize in membrane domains, to support rolling on P-selectin, and to signal through spleen tyrosine kinase (Syk). We generated "DeltaCD" mice that express PSGL-1 without the cytoplasmic domain. Unexpectedly, neutrophils from these mice localized PSGL-1 normally in microvilli, uropods, and lipid rafts. DeltaCD neutrophils expressed less PSGL-1 on their surfaces because of inefficient export from the endoplasmic reticulum. Limited digestion of wild-type neutrophils with O-sialoglycoprotein endopeptidase was used to reduce the PSGL-1 density to that on DeltaCD neutrophils. At matched PSGL-1 densities, both DeltaCD and wild-type neutrophils rolled similarly on P-selectin. However, DeltaCD neutrophils rolling on P-selectin did not trigger Syk-dependent activation of LFA-1 to slow rolling on ICAM-1. These data demonstrate that the PSGL-1 cytoplasmic domain is dispensable for leukocyte rolling on P-selectin but is essential to activate beta2 integrins to slow rolling on ICAM-1.
- Subjects :
- Amino Acid Sequence
Animals
CD18 Antigens physiology
Hemorheology
In Vitro Techniques
Intercellular Adhesion Molecule-1 physiology
Intracellular Signaling Peptides and Proteins physiology
Membrane Glycoproteins deficiency
Membrane Glycoproteins genetics
Membrane Microdomains metabolism
Mice
Mice, Knockout
Mice, Transgenic
Microvilli metabolism
Models, Biological
Models, Molecular
Molecular Sequence Data
P-Selectin physiology
Peptide Fragments chemistry
Peptide Fragments genetics
Peptide Fragments physiology
Protein Structure, Tertiary
Protein-Tyrosine Kinases physiology
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins metabolism
Signal Transduction
Syk Kinase
Leukocyte Rolling physiology
Membrane Glycoproteins chemistry
Membrane Glycoproteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 112
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 18550846
- Full Text :
- https://doi.org/10.1182/blood-2008-04-149468