4.7 Article

Signal-dependent distribution of cell surface P-selectin in clathrin-coated pits affects leukocyte rolling under flow

期刊

JOURNAL OF CELL BIOLOGY
卷 163, 期 6, 页码 1385-1395

出版社

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200307178

关键词

selectin; endocytosis; endothelial cell; thrombin; RhoA

资金

  1. NCRR NIH HHS [P20 RR015577] Funding Source: Medline
  2. NHLBI NIH HHS [R01 HL034363, R37 HL034363, HL 34363] Funding Source: Medline

向作者/读者索取更多资源

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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