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Quantitative elucidation of a distinct spatial gradient-sensing mechanism in fibroblasts

Quantitative elucidation of a distinct spatial gradient-sensing mechanism in fibroblasts Migration of eukaryotic cells toward a chemoattractant often relies on their ability to distinguish receptor-mediated signaling at different subcellular locations, a phenomenon known as spatial sensing. A prominent example that is seen during wound healing is fibroblast migration in platelet-derived growth factor (PDGF) gradients. As in the well-characterized chemotactic cells Dictyostelium discoideum and neutrophils, signaling to the cytoskeleton via the phosphoinositide 3-kinase pathway in fibroblasts is spatially polarized by a PDGF gradient; however, the sensitivity of this process and how it is regulated are unknown. Through a quantitative analysis of mathematical models and live cell total internal reflection fluorescence microscopy experiments, we demonstrate that PDGF detection is governed by mechanisms that are fundamentally different from those in D. discoideum and neutrophils. Robust PDGF sensing requires steeper gradients and a much narrower range of absolute chemoattractant concentration, which is consistent with a simpler system lacking the feedback loops that yield signal amplification and adaptation in amoeboid cells. Footnotes Abbreviations used in this paper: AktPH, pleckstrin homology domain of Akt; GPCR, G protein–coupled receptor; OG, Oregon green; PI, phosphoinositide; TIRF, total internal reflection fluorescence. Submitted: 6 September 2005 Accepted: 27 October 2005 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

Quantitative elucidation of a distinct spatial gradient-sensing mechanism in fibroblasts

Schneider, Ian C.; Haugh, Jason M.
The Journal of Cell Biology , Volume 171 (5): 883 – Dec 5, 2005
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References (51)

Publisher
Rockefeller University Press
Copyright
Copyright © 2005, by The Rockefeller University Press
ISSN
0021-9525
eISSN
1540-8140
DOI
10.1083/jcb.200509028
pmid
16314431
Publisher site
See Article on Publisher Site

Abstract

Migration of eukaryotic cells toward a chemoattractant often relies on their ability to distinguish receptor-mediated signaling at different subcellular locations, a phenomenon known as spatial sensing. A prominent example that is seen during wound healing is fibroblast migration in platelet-derived growth factor (PDGF) gradients. As in the well-characterized chemotactic cells Dictyostelium discoideum and neutrophils, signaling to the cytoskeleton via the phosphoinositide 3-kinase pathway in fibroblasts is spatially polarized by a PDGF gradient; however, the sensitivity of this process and how it is regulated are unknown. Through a quantitative analysis of mathematical models and live cell total internal reflection fluorescence microscopy experiments, we demonstrate that PDGF detection is governed by mechanisms that are fundamentally different from those in D. discoideum and neutrophils. Robust PDGF sensing requires steeper gradients and a much narrower range of absolute chemoattractant concentration, which is consistent with a simpler system lacking the feedback loops that yield signal amplification and adaptation in amoeboid cells. Footnotes Abbreviations used in this paper: AktPH, pleckstrin homology domain of Akt; GPCR, G protein–coupled receptor; OG, Oregon green; PI, phosphoinositide; TIRF, total internal reflection fluorescence. Submitted: 6 September 2005 Accepted: 27 October 2005

Journal

The Journal of Cell Biology – Rockefeller University Press

Published: Dec 5, 2005

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