A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediated egress. Export

@article{citeulike:1460366, abstract = {Recent observations using multiphoton intravital microscopy (MP-IVM) have uncovered an unexpectedly high lymphocyte motility within peripheral lymph nodes (PLNs). Lymphocyte-expressed intracellular signaling molecules governing interstitial movement remain largely unknown. Here, we used MP-IVM of murine PLNs to examine interstitial motility of lymphocytes lacking the Rac guanine exchange factor DOCK2 and phosphoinositide-3-kinase (PI3K)gamma, signaling molecules that act downstream of G protein-coupled receptors, including chemokine receptors (CKRs). T and B cells lacking DOCK2 alone or DOCK2 and PI3Kgamma displayed markedly reduced motility inside T cell area and B cell follicle, respectively. Lack of PI3Kgamma alone had no effect on migration velocity but resulted in increased turning angles of T cells. As lymphocyte egress from PLNs requires the sphingosine-1-phosphate (S1P) receptor 1, a G(alphai) protein-coupled receptor similar to CKR, we further analyzed whether DOCK2 and PI3Kgamma contributed to S1P-triggered signaling events. S1P-induced cell migration was significantly reduced in T and B cells lacking DOCK2, whereas T cell-expressed PI3Kgamma contributed to F-actin polymerization and protein kinase B phosphorylation but not migration. These findings correlated with delayed lymphocyte egress from PLNs in the absence of DOCK2 but not PI3Kgamma, and a markedly reduced cell motility of DOCK2-deficient T cells in close proximity to efferent lymphatic vessels. In summary, our data support a central role for DOCK2, and to a lesser extent T cell-expressed PI3Kgamma, for signal transduction during interstitial lymphocyte migration and S1P-mediated egress.}, address = {Theodor Kocher Institute, University of Bern, CH-3012 Bern, Switzerland.}, author = {Nombela-Arrieta, C. and Mempel, T. R. and Soriano, S. F. and Mazo, I. and Wymann, M. P. and Hirsch, E. and Mart\'{\i}nez-A, C. and Fukui, Y. and von Andrian, U. H. and Stein, J. V.}, citeulike-article-id = {1460366}, citeulike-linkout-0 = {http://dx.doi.org/10.1084/jem.20061780}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17325199}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17325199}, day = {19}, doi = {10.1084/jem.20061780}, issn = {0022-1007}, journal = {J Exp Med}, keywords = {dock2, p110g}, month = {March}, number = {3}, pages = {497--510}, posted-at = {2007-07-17 01:18:07}, priority = {2}, title = {A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediated egress.}, url = {http://dx.doi.org/10.1084/jem.20061780}, volume = {204}, year = {2007} }

TY - JOUR ID - citeulike:1460366 L3 - citeulike-article-id:1460366 N2 - Recent observations using multiphoton intravital microscopy (MP-IVM) have uncovered an unexpectedly high lymphocyte motility within peripheral lymph nodes (PLNs). Lymphocyte-expressed intracellular signaling molecules governing interstitial movement remain largely unknown. Here, we used MP-IVM of murine PLNs to examine interstitial motility of lymphocytes lacking the Rac guanine exchange factor DOCK2 and phosphoinositide-3-kinase (PI3K)gamma, signaling molecules that act downstream of G protein-coupled receptors, including chemokine receptors (CKRs). T and B cells lacking DOCK2 alone or DOCK2 and PI3Kgamma displayed markedly reduced motility inside T cell area and B cell follicle, respectively. Lack of PI3Kgamma alone had no effect on migration velocity but resulted in increased turning angles of T cells. As lymphocyte egress from PLNs requires the sphingosine-1-phosphate (S1P) receptor 1, a G(alphai) protein-coupled receptor similar to CKR, we further analyzed whether DOCK2 and PI3Kgamma contributed to S1P-triggered signaling events. S1P-induced cell migration was significantly reduced in T and B cells lacking DOCK2, whereas T cell-expressed PI3Kgamma contributed to F-actin polymerization and protein kinase B phosphorylation but not migration. These findings correlated with delayed lymphocyte egress from PLNs in the absence of DOCK2 but not PI3Kgamma, and a markedly reduced cell motility of DOCK2-deficient T cells in close proximity to efferent lymphatic vessels. In summary, our data support a central role for DOCK2, and to a lesser extent T cell-expressed PI3Kgamma, for signal transduction during interstitial lymphocyte migration and S1P-mediated egress. IS - 3 JF - J Exp Med SN - 0022-1007 AD - Theodor Kocher Institute, University of Bern, CH-3012 Bern, Switzerland. EP - 510 TI - A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediated egress. VL - 204 SP - 497 KW - dock2 KW - p110g AU - Nombela-Arrieta, C AU - Mempel, TR AU - Soriano, SF AU - Mazo, I AU - Wymann, MP AU - Hirsch, E AU - Martínez-A, C AU - Fukui, Y AU - von Andrian, UH AU - Stein, JV PY - 2007/03/19/ UR - http://dx.doi.org/10.1084/jem.20061780 ER -