Journal
JOURNAL OF CELL BIOLOGY
Volume 163, Issue 6, Pages 1385-1395Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200307178
Keywords
selectin; endocytosis; endothelial cell; thrombin; RhoA
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Funding
- NCRR NIH HHS [P20 RR015577] Funding Source: Medline
- NHLBI NIH HHS [R01 HL034363, R37 HL034363, HL 34363] Funding Source: Medline
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Flowing leukocytes roll on P-selectin that is mobilized from secretory granules to the surfaces of endothelial cells after stimulation with histamine or thrombin. Before it is internalized, P-selectin clusters in clathrin-coated pits, which enhances its ability to support leukocyte rolling. We found that thrombin and histamine induced comparable exocytosis of P-selectin on endothelial cells. However, compared with histamine, thrombin decreased the recruitment of P-selectin into clathrin-coated pits, slowed the internalization of P-selectin, and reduced the number and stability of neutrophils rolling on P-selectin. Significantly more RhoA was activated in thrombin- than in histamine-stimulated endothelial cells. Inhibitors of RhoA or its effector, Rho kinase, reversed thrombin's ability to inhibit the internalization and adhesive function of P-selectin in endothelial cells. Experiments with transfected cells confirmed that the inhibitory actions of thrombin and Rho kinase on P-selectin required its cytoplasmic domain. Thus, a signaling event affects both the function and clearance of a protein that enters the constitutive clathrin-mediated endocytic pathway.
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