Journal ArticleDOI
Membrane lipids, EGF receptors, and intracellular signals colocalize and are polarized in epithelial cells moving directionally in a physiological electric field
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TLDR
A model in which EF‐polarized membrane lipid domains and EGF receptors cause asymmetric signaling through MAP kinase, which drives directional cell migration is proposed, and a comparison is made with the mechanisms underpinning chemotaxis.Abstract:
Directed cell migration is essential for tissue formation, inflammation, and wound healing. Chemotaxis plays a major role in these situations and is underpinned by asymmetric intracellular signaling. Endogenous electric fields (EFs) are common where cell movement occurs, such as in wound healing, and cells respond to electric field gradients by reorienting and migrating directionally (galvanotaxis/electrotaxis). We show that a physiological EF redistributed both EGF (epidermal growth factor) receptors and detergent-insoluble membrane lipids asymmetrically, leading to cathodal polarization and enhanced activation of the MAP kinase, ERK1/2. This induced leading-edge actin polymerization in directionally migrating mammalian epithelial cells. Inhibiting the EGF receptor-MAP kinase signaling pathway significantly decreased leading edge actin asymmetry and directional migration. We propose a model in which EF-polarized membrane lipid domains and EGF receptors cause asymmetric signaling through MAP kinase, which drives directional cell migration. A comparison is made with the mechanisms underpinning chemotaxis.read more
Citations
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Journal ArticleDOI
Epidermal growth factor receptor: mechanisms of activation and signalling.
Robert N. Jorissen,Francesca Walker,Francesca Walker,Normand Pouliot,Thomas P. J. Garrett,Thomas P. J. Garrett,Colin W. Ward,Colin W. Ward,Antony W. Burgess,Antony W. Burgess +9 more
TL;DR: The structure and function of the EGFR is reviewed, from ligand binding to the initiation of intracellular signalling pathways that lead to changes in the biochemical state of the cell.
Journal ArticleDOI
Controlling Cell Behavior Electrically: Current Views and Future Potential
TL;DR: This review aims to resolve issues by describing the historical context of bioelectricity, the fundamental principles of physics and physiology responsible for DC electric fields within cells and tissues, the cellular mechanisms for the effects of small electric fields on cell behavior, and the clinical potential for electric field treatment of damaged tissues.
Journal ArticleDOI
Electrical fields in wound healing-An overriding signal that directs cell migration.
TL;DR: Clinically, it is highly desirable to develop practical and reliable technologies for wound healing management exploiting the electric signaling, and genetic manipulation of PI3 kinase/Pten and integrin beta4 demonstrated the importance of those molecules.
Journal ArticleDOI
Electrical stimulation directly induces pre-angiogenic responses in vascular endothelial cells by signaling through VEGF receptors
TL;DR: It is reported that applied electric fields of small physiological magnitude directly stimulate VEGF production by endothelial cells in culture without the presence of any other cell type, indicating that endogenous EFs might play a role in angiogenesis in vivo by stimulating the V EGF receptor signaling pathway, to induce key pre-angiogenic responses.
Journal ArticleDOI
Electromagnetic effects - From cell biology to medicine.
TL;DR: This review tries to link areas of EF, MF and EMF research to thermodynamics and quantum physics, approaches that will produce novel insights into cell biology.
References
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Journal ArticleDOI
Regulation of Cell Motility by Mitogen-activated Protein Kinase
Richard L. Klemke,Shuang Cai,Ana L. Giannini,Patricia J. Gallagher,Primal de Lanerolle,David A. Cheresh +5 more
TL;DR: In vitro results support evidence that ERK-phosphorylated MLCK has an increased capacity to phosphorylate MLC and shows increased sensitivity to calmodulin, and define a signaling pathway directly downstream of MAP kinase, influencing cell migration on the extracellular matrix.
Journal ArticleDOI
A Cell's Sense of Direction
TL;DR: In eukaryotic cells directional sensing is mediated by heterotrimeric guanine nucleotide-binding protein (G protein)-linked signaling pathways and the cell senses direction by spatially regulating the activity of the signal transduction pathway.
Journal ArticleDOI
Polarization of Chemoattractant Receptor Signaling During Neutrophil Chemotaxis
TL;DR: Morphologic polarity is necessary for chemotaxis of mammalian cells and the pleckstrin homology domain of the AKT protein kinase, tagged with the green fluorescent protein (PHAKT-GFP), was expressed in neutrophils to probe intracellular signals responsible for this asymmetry.
Journal ArticleDOI
G Protein Signaling Events Are Activated at the Leading Edge of Chemotactic Cells
Carole A. Parent,Brenda J. Blacklock,Wendy M. Froehlich,Douglas B. Murphy,Peter N. Devreotes +4 more
TL;DR: It is proposed that localized activation, transmitted by the recruitment of cytosolic proteins, may be a general mechanism for gradient sensing by G protein-linked chemotactic systems including those involvingChemotactic cytokines in leukocytes.
Journal ArticleDOI
Segregation of leading-edge and uropod components into specific lipid rafts during T cell polarization
Concepción Gómez-Moutón,José Luis Abad,Emilia Mira,Rosa Ana Lacalle,Eduard Gallardo,Sonia Jiménez-Baranda,Isabel Illa,Antonio Bernad,Santos Mañes,Carlos Martínez-A +9 more
TL;DR: The data suggest that raft partitioning is a major determinant for protein redistribution in polarized T cells, as ectopic expression of raft-associated proteins results in their asymmetric redistribution, whereas non-raft-partitioned mutants of these proteins are distributed homogeneously in the polarized cell membrane.