| First Author | Shao B | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 23 | Pages | 19585-98 |
| PubMed ID | 22511754 | Mgi Jnum | J:186204 |
| Mgi Id | MGI:5431187 | Doi | 10.1074/jbc.M112.361519 |
| Citation | Shao B, et al. (2012) Signal-dependent slow leukocyte rolling does not require cytoskeletal anchorage of P-selectin glycoprotein ligand-1 (PSGL-1) or integrin alphaLbeta2. J Biol Chem 287(23):19585-98 |
| abstractText | In inflamed venules, neutrophils roll on P- or E-selectin, engage P-selectin glycoprotein ligand-1 (PSGL-1), and signal extension of integrin alpha(L)beta(2) in a low affinity state to slow rolling on intercellular adhesion molecule-1 (ICAM-1). Cytoskeleton-dependent receptor clustering often triggers signaling, and it has been hypothesized that the cytoplasmic domain links PSGL-1 to the cytoskeleton. Chemokines cause rolling neutrophils to fully activate alpha(L)beta(2), leading to arrest on ICAM-1. Cytoskeletal anchorage of alpha(L)beta(2) has been linked to chemokine-triggered extension and force-regulated conversion to the high affinity state. We asked whether PSGL-1 must interact with the cytoskeleton to initiate signaling and whether alpha(L)beta(2) must interact with the cytoskeleton to extend. Fluorescence recovery after photobleaching of transfected cells documented cytoskeletal restraint of PSGL-1. The lateral mobility of PSGL-1 similarly increased by depolymerizing actin filaments with latrunculin B or by mutating the cytoplasmic tail to impair binding to the cytoskeleton. Converting dimeric PSGL-1 to a monomer by replacing its transmembrane domain did not alter its mobility. By transducing retroviruses expressing WT or mutant PSGL-1 into bone marrow-derived macrophages from PSGL-1-deficient mice, we show that PSGL-1 required neither dimerization nor cytoskeletal anchorage to signal beta(2) integrin-dependent slow rolling on P-selectin and ICAM-1. Depolymerizing actin filaments or decreasing actomyosin tension in neutrophils did not impair PSGL-1- or chemokine-mediated integrin extension. Unlike chemokines, PSGL-1 did not signal cytoskeleton-dependent swing out of the beta(2)-hybrid domain associated with the high affinity state. The cytoskeletal independence of PSGL-1-initiated, alpha(L)beta(2)-mediated slow rolling differs markedly from the cytoskeletal dependence of chemokine-initiated, alpha(L)beta(2)-mediated arrest. |
