A novel role for FGF and extracellular signal-regulated kinase in gap junction-mediated intercellular communication in the lens.
Gap junction-mediated intercellular coupling is higher in the equatorial region of the lens than at either pole, a property believed to be essential for lens transparency. We show that fibroblast growth factor (FGF) upregulates gap junctional intercellular dye transfer in primary cultures of embryonic chick lens cells without detectably increasing either gap junction protein (connexin) synthesis or assembly. Insulin and insulin-like growth factor 1, as potent as FGF in inducing lens cell differentiation, had no effect on gap junctions. FGF induced sustained activation of extracellular signal-regulated kinase (ERK) in lens cells, an event necessary and sufficient to increase gap junctional coupling. We also identify vitreous humor as an in vivo source of an FGF-like intercellular communication-promoting activity and show that FGF-induced ERK activation in the intact lens is higher in the equatorial region than in polar and core fibers. These findings support a model in which regional differences in FGF signaling through the ERK pathway lead to the asymmetry in gap junctional coupling required for proper lens function. Our results also identify upregulation of intercellular communication as a new function for sustained ERK activation and change the current paradigm that ERKs only negatively regulate gap junction channel activity.
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Molecular Medicine Division, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.
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D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D002478:Cells, Cultured; D002642:Chick Embryo; D017630:Connexins / Q000378:metabolism; D004789:Enzyme Activation; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D017629:Gap Junctions; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D014822:Vitreous Body / Q000378:metabolism
D017630:Connexins; D007328:Insulin; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D020928:Mitogen-Activated Protein Kinases