Regulation of Gap Junction Coupling Through the Neuronal Connexin Cx35 by Nitric Oxide and cGMP |
| |
| Authors: | Leena S. Patel Cheryl K. Mitchell William P. Dubinsky John O'Brien |
| |
| Affiliation: | a Department of Ophthalmology and Visual Science, University of Texas Health Science Center, Houstonb Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houstonc The Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston |
| |
| Abstract: | Gap-junctional coupling among neurons is subject to regulation by a number of neurotransmitters including nitric oxide. We studied the mechanisms by which NO regulates coupling in cells expressing Cx35, a connexin expressed in neurons throughout the central nervous system. NO donors caused potent uncoupling of HeLa cells stably transfected with Cx35. This effect was mimicked by Bay 21-4272, an activator of guanylyl cyclase. A pharmacological analysis indicated that NO-induced uncoupling involved both PKG-dependent and PKG-independent pathways. PKA was involved in both pathways, suggesting that PKG-dependent uncoupling may be indirect. In vitro, PKG phosphorylated Cx35 at three sites: Ser110, Ser276, and Ser289. A mutational analysis indicated that phosphorylation on Ser110 and Ser276, sites previously shown also to be phosphorylated by PKA, had a significant influence on regulation. Ser289 phosphorylation had very limited effects. We conclude that NO can regulate coupling through Cx35 and that regulation is indirect in HeLa cells. |
| |
| Keywords: | nitric oxide connexin35 connexin36 phosphorylation HeLa cells |
| 本文献已被 InformaWorld 等数据库收录！ |
|
