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Sphingosine 1‐phosphate mediates chemotaxis of human primary fibroblasts via the S1P‐receptor subtypes S1P 1 and S1P 3 and Smad‐signalling
Author(s) -
Gil Pilar Rivera,
Japtok Lukasz,
Kleuser Burkhard
Publication year - 2010
Publication title -
cytoskeleton
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.95
H-Index - 86
eISSN - 1949-3592
pISSN - 1949-3584
DOI - 10.1002/cm.20486
Subject(s) - chemotaxis , biology , microbiology and biotechnology , sphingosine 1 phosphate , crosstalk , focal adhesion , sphingosine , downregulation and upregulation , motility , smad2 protein , sphingosine 1 phosphate receptor , signal transduction , smad , receptor , chemokinesis , sphingosine kinase , biochemistry , physics , gene , optics
The sphingolipid sphingosine 1‐phosphate (S1P) induces chemotaxis of primary fibroblasts. Thus, S1P exhibited a chemotactic effect in a concentration‐dependent manner from 10 −6 to 10 −9 M; higher concentrations resulted in a loss of migration, and lower amounts were ineffective to evoke movement toward a concentration gradient of S1P. In congruence with the migratory response, S1P caused an extension of lamellipodia at the cell periphery of human fibroblasts and a rearrangement of the cytoskeleton. These effects were visible by phalloidin staining of actin filaments as well as focal adhesion turnover. As the molecular mechanism of S1P‐mediated migration of fibroblasts has not been well characterized, we investigated whether S1P‐receptors are involved in the chemotactic response. Indeed, inhibition of G i signalling markedly reduced motility towards S1P, suggesting an involvement of S1P‐receptor subtypes. Moreover, downregulation of S1P 1 and S1P 3 indicated that these S1P‐receptor subtypes are responsible for the chemotactic action of the bioactive sphingolipid. After having identified a crosstalk between Smad‐proteins and S1P‐signalling, we investigated whether Smad‐activation is involved in the chemotactic response induced by S1P. Indeed S1P caused a Smad‐activation via the S1P receptor subtypes S1P 1 and S1P 3 . Moreover, downregulation of Smad3 diminished the ability of S1P to mediate a chemotactic response in fibroblasts, indicating a crosstalk between TGF‐β‐ and S1P‐signalling. © 2010 Wiley‐Liss, Inc.