TY - JOUR
T1 - Sphingosine 1-phosphate-induced motility and endocytosis of dendritic cells is regulated by SWAP-70 through RhoA
AU - Ocaña-Morgner, Carlos
AU - Reichardt, Peter
AU - Chopin, Michaël
AU - Braungart, Sarah
AU - Wahren, Christine
AU - Gunzer, Matthias
AU - Jessberger, Rolf
PY - 2011/5/1
Y1 - 2011/5/1
N2 - The phospholipid mediator sphingosine 1-phosphate (S1P) enhances motility and endocytosis of mature dendritic cells (DCs). We show that in vitro migration of Swap-70-/- bone marrow-derived DCs (BMDCs) in response to S1P and S1P-induced upregulation of endocytosis are significantly reduced. S1P-stimulated movement of Swap-70-/- BMDCs, specifically retraction of their trailing edge, in a collagen three-dimensional environment is impaired. These in vitro observations correlate with delayed entry into lymphatic vessels and migration to lymph nodes of skin DCs in Swap-70-/- mice. Expression of S1P receptors (S1P1-3) by wild-type and Swap-70 -/- BMDCs is similar, but Swap-70-/- BMDCs fail to activate RhoA and to localize Rac1 and RhoA into areas of actin polymerization after S1P stimulus. The Rho-activating G protein Gai interacts with SWAP-70, which also supports the localization of Gα13 to membrane rafts in BMDCs. LPS-matured Swap-70-/- BMDCs contain significantly more active RhoA than wild-type DCs. Preinhibition of Rho activation restored migration to S1P, S1P-induced upregulation of endocytosis in mature Swap-70-/- BMDCs, and localization of Gα13 to membrane rafts. These data demonstrate SWAP-70 as a novel regulator of S1P signaling necessary for DC motility and endocytosis.
AB - The phospholipid mediator sphingosine 1-phosphate (S1P) enhances motility and endocytosis of mature dendritic cells (DCs). We show that in vitro migration of Swap-70-/- bone marrow-derived DCs (BMDCs) in response to S1P and S1P-induced upregulation of endocytosis are significantly reduced. S1P-stimulated movement of Swap-70-/- BMDCs, specifically retraction of their trailing edge, in a collagen three-dimensional environment is impaired. These in vitro observations correlate with delayed entry into lymphatic vessels and migration to lymph nodes of skin DCs in Swap-70-/- mice. Expression of S1P receptors (S1P1-3) by wild-type and Swap-70 -/- BMDCs is similar, but Swap-70-/- BMDCs fail to activate RhoA and to localize Rac1 and RhoA into areas of actin polymerization after S1P stimulus. The Rho-activating G protein Gai interacts with SWAP-70, which also supports the localization of Gα13 to membrane rafts in BMDCs. LPS-matured Swap-70-/- BMDCs contain significantly more active RhoA than wild-type DCs. Preinhibition of Rho activation restored migration to S1P, S1P-induced upregulation of endocytosis in mature Swap-70-/- BMDCs, and localization of Gα13 to membrane rafts. These data demonstrate SWAP-70 as a novel regulator of S1P signaling necessary for DC motility and endocytosis.
UR - http://www.scopus.com/inward/record.url?scp=79955531473&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1003461
DO - 10.4049/jimmunol.1003461
M3 - Article
C2 - 21421853
AN - SCOPUS:79955531473
SN - 0022-1767
VL - 186
SP - 5345
EP - 5355
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -