Ca2+ influx is an essential component of the positive-feedback loop that maintains leading-edge structure and activity in macrophages.

作者: J. H. Evans , J. J. Falke

DOI: 10.1073/PNAS.0707719104

关键词:

摘要: In migrating eukaryotic cells, phosphatidylinositol 3-kinase (PI3K), filamentous actin (F-actin), and monomeric Rho GTPases are key components of a complex positive-feedback system that maintains amplifies phosphatidylinositol-3,4,5-trisphosphate signal at the leading edge cell. This lipid is required for cell polarization movement. leukocytes Dictyostelium, activation or inhibition any one these leads to inhibition, respectively, others via undefined feedback interactions. The role Ca2+ signals in controversial, there has been no indication participates positive feedback. Here, we demonstrate an extracellular influx spontaneously polarized macrophages. Inhibition loss leading-edge PI3K activity, disassembly F-actin, cessation ruffling, decay chemoattractant signals. Conversely, increasing cytosolic enhances membrane F-actin accumulation. Overall, findings essential component, together with cycle structure ruffling activity supports response. Strikingly, Ca2+-sensitive enzyme protein kinase Cα (PKCα) enriched edge, its enrichment sensitive blockade influx, depolymerization. These support working hypothesis local, recruits PKCα as central player loop.

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