| First Author | Boswell BA | Year | 2010 |
| Journal | Mol Biol Cell | Volume | 21 |
| Issue | 10 | Pages | 1686-97 |
| PubMed ID | 20357001 | Mgi Jnum | J:165066 |
| Mgi Id | MGI:4836135 | Doi | 10.1091/mbc.E10-01-0055 |
| Citation | Boswell BA, et al. (2010) Regulation of lens gap junctions by Transforming Growth Factor beta. Mol Biol Cell 21(10):1686-97 |
| abstractText | Gap junction-mediated intercellular communication (GJIC) is essential for the proper function of many organs, including the lens. GJIC in lens epithelial cells is increased by FGF in a concentration-dependent process that has been linked to the intralenticular gradient of GJIC required for lens transparency. Unlike FGF, elevated levels of TGF-beta are associated with lens dysfunction. We show that TGF-beta1 or -2 up-regulates dye coupling in serum-free primary cultures of chick lens epithelial cells (dissociated cell-derived monolayer cultures [DCDMLs]) via a mechanism distinct from that utilized by other growth factors. Remarkably, the ability of TGF-beta and of FGF to up-regulate GJIC is abolished if DCDMLs are simultaneously exposed to both factors despite undiminished cell-cell contact. This reduction in dye coupling is attributable to an inhibition of gap junction assembly. Connexin 45.6, 43, and 56-containing gap junctions are restored, and intercellular dye coupling is increased, if the activity of p38 kinase is blocked. Our data reveal a new type of cross-talk between the FGF and TGF-beta pathways, as well as a novel role for TGF-beta and p38 kinase in the regulation of GJIC. They also provide an explanation for how pathologically increased TGF-beta signaling could contribute to cataract formation. |
