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Vol. 20, Issue 10, 2582-2592, May 15, 2009

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Interaction between Connexin50 and Mitogen-activated Protein Kinase Signaling in Lens Homeostasis

Teresa I. Shakespeare^*, Caterina Sellitto^*, Leping Li^*, Clio Rubinos, Xiaohua Gong, Miduturu Srinivas, and Thomas W. White^*

*Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794-8661; Department of Biological Sciences, SUNY College of Optometry, New York, NY 10036; and Department of Optometry, University of California, Berkeley, CA 94720-2020

Submitted January 2, 2009; Revised March 13, 2009; Accepted March 13, 2009
Monitoring Editor: Benjamin Margolis

Both connexins and signal transduction pathways have been independently shown to play critical roles in lens homeostasis, but little is known about potential cooperation between these two intercellular communication systems. To investigate whether growth factor signaling and gap junctional communication interact during the development of lens homeostasis, we examined the effect of mitogen-activated protein kinase (MAPK) signaling on coupling mediated by specific lens connexins by using a combination of in vitro and in vivo assays. Activation of MAPK signaling pathways significantly increased coupling provided by Cx50, but not Cx46, in paired Xenopus laevis oocytes in vitro, as well as between freshly isolated lens cells in vivo. Constitutively active MAPK signaling caused macrophthalmia, cataract, glucose accumulation, vacuole formation in differentiating fibers, and lens rupture in vivo. The specific removal or replacement of Cx50, but not Cx46, ameliorated all five pathological conditions in transgenic mice. These results indicate that MAPK signaling specifically modulates coupling mediated by Cx50 and that gap junctional communication and signal transduction pathways may interact in osmotic regulation during postnatal fiber development.

Address correspondence to: Thomas W. White (thomas.white{at}sunysb.edu)