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...

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Bibliographic Details
Published in:The Journal of cell biology 2005-12, Vol.171 (5), p.883-892
Main Authors: Schneider, Ian C, Haugh, Jason M
Format: Article
Language:English
Subjects:
3T3 Cells
Algorithms
Animals
Cell adhesion & migration
Cell membranes
Cells
Cellular biology
Chemotaxis
Chemotaxis - physiology
Dictyostelium - cytology
Dictyostelium - physiology
Dictyostelium discoideum
Eukaryotes
Fibroblasts
Fibroblasts - physiology
Fluorescence
Kinetics
Memory interference
Mice
Modeling
Models, Biological
Neutrophils
Neutrophils - physiology
Phosphatidylinositol 3-Kinases - metabolism
Platelet-Derived Growth Factor - metabolism
Receptors
Signal Transduction
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200509028