Abstracts (complete list) - Wissenschaft Online

Martin Klemke, Elisabeth Kramer, Guido Wabnitz, Mathias Konstandin, Yvonne
Samstag
The chemokine SDF-1α induces dephosphorylation of the actin
remodelling protein cofilin via a Gi/Ras/MEK pathway in
primary human T cells
The homeostatic and inflammatory migration of T cells is mediated via several
chemokines which act on different G protein-coupled receptors (GPCR). CXCR4, the
receptor for the chemokine SDF-1α, is expressed by most human T cell subpopulations.
SDF-1α treatment activates multiple downstream signaling pathways, e.g. the MEK- and
PI3K-pathways, which finally leads to reorganization of the actin cytoskeleton. However,
the exact molecular mechanisms of CXCR4-mediated actin reorganization in primary
human T cells are still unclear. The actin-binding protein cofilin is a central regulator of
actin dynamics through its actin depolymerizing and severing activity. In resting human
T cells, most of the cofilin molecules are inactivated through phosphorylation at Ser3.
Here we show, that cofilin is dephosphorylated/activated upon treatment of primary
human T cells with SDF-1α. This dephosphorylation is mediated via a Gi/Ras/MEK
pathway, whereas the PI3K pathway is not involved. Interference with the cofilin
dephosphorylation pathway by inhibition of MEK results in enhanced SDF-1α-induced
actin polymerization and reduced velocity during SDF-1α mediated cell migration. These
data imply that dephosphorylation/activation of cofilin through a Gi/Ras/MEK signaling
pathway is necessary for the proper reorganization of the actin cytoskeleton during SDF-
1α mediated migration of primary human T cells.