FASEB J. Avanti Polar Lipids
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The FASEB Journal Express Article doi:10.1096/fj.01-0811fje
Published online April 10, 2002

Membrane lipids, EGF receptors, and intracellular signals colocalize and are polarized in epithelial cells moving directionally in a physiological electric field

Min Zhao, Jin Pu, John V. Forrester, and Colin D. McCaig

E-mail contact: m.zhao{at}abdn.ac.uk, c.mccaig{at}abdn.ac.uk

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.

Key words: directional cell migration · electric fields · EGF receptor · MAP kinase ERK1/2 · wound healing · eletrotaxis/galvanotaxis




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