Chemokine stimulation of human peripheral blood T lymphocytes induces rapid dephosphorylation of ERM proteins, which facilitates loss of microvilli and polarization
| Autor: | Ruchika Nijhara, Stanley L. Erlandsen, Martin J. Brown, Stephen Shaw, John A. Hallam, Jérôme Delon, Kenneth M. Yamada, Michelle Gignac, Michael J. Kruhlak |
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| Rok vydání: | 2003 |
| Předmět: |
Chemokine
Stromal cell T-Lymphocytes Moesin Immunology Biochemistry Dephosphorylation Ezrin Radixin Humans Phosphorylation Cytoskeleton Microvilli biology Microfilament Proteins Cell Polarity Membrane Proteins Blood Proteins Cell Biology Hematology Phosphoproteins Chemokine CXCL12 Cell biology Cytoskeletal Proteins Kinetics biology.protein Chemokines Chemokines CXC |
| Zdroj: | Blood. 102:3890-3899 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Lymphocyte microvilli mediate initial rolling-adhesion along endothelium but are lost during transmigration from circulation to tissue. However, the mechanism for resorption of lymphocyte microvilli remains unexplored. We show that chemokine stimulation of human peripheral blood T (PBT) cells is sufficient to induce rapid resorption of microvilli. Microvilli in other cells are regulated by ezrin/radixin/moesin (ERM) proteins, which link the plasma membrane to the cortical F-actin cytoskeleton; maintenance of these linkages requires ERM activation, reflected by phosphorylation at a specific carboxy-terminal threonine residue. Carboxyphosphorylated-ERM (cpERM) proteins in resting PBT cells show a punctate peripheral distribution consistent with localization to microvilli. cpERM dephosphorylation begins within seconds of stimulation by chemokines (stromal derived factor 1α [SDF-1α] or secondary lymphoid tissue cytokine), and ERM proteins lose their punctate distribution with kinetics paralleling the loss of microvilli. The cpERM proteins are preferentially associated with the cytoskeleton at rest and this association is lost with chemokine-induced dephosphorylation. Transfection studies show that a dominant-negative ERM construct destroys microvilli, whereas a construct mimicking cpERM facilitates formation of microvilli, retards chemokine-induced loss of microvilli, and markedly impairs chemokine-induced polarization. Thus, chemokine induces rapid dephosphorylation and inactivation of cpERM, which may in turn facilitate 2 aspects of cytoskeletal reorganization involved in lymphocyte recruitment: loss of microvilli and polarization. |
| Databáze: | OpenAIRE |
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