Electrical synapses between neurons are formed by gap junction channels, through which ions and metabolites pass directly from one cell to the next. Recent evidence indicates that other proteins are associated with connexins at gap junctions, and we have termed this macromolecular complex the Nexus. We hypothesize that the Nexus components may regulate both the properties of the gap junction channels and also may function in intracellular signal transduction. A new gap junction protein, connexin36, has been identified that is largely restricted in its expression to neurons, and we have shown that the channels formed by this connexin have properties that seem to uniquely suit it as a neuronal connexin. The goals of this grant application are to characterize the gating, permeability and conductance properties with regard to the protein domains involved, to identify other proteins in brain and neuron lysates that bind to connexin36, measure the strengths of interaction using surface plasmon resonance, and perform physiological experiments on neuron-like cells to determine the effects of Cx36 expression on neuronal differentiation and gene expression patterns. In addition, a major goal of this application is to obtain structural information using spectroscopic methods regarding domains of Cx36 that interact with each other and with other proteins. These studies use a multidisciplinary approach directed at exploring a new concept in the field and as such are expected to lead to novel understanding of regulation and roles of gap junctions in the nervous system.
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| Thi, Mia M; Spray, David C; Hanani, Menachem (2008) Aquaporin-4 water channels in enteric neurons. J Neurosci Res 86:448-56 |
| Alev, Cantas; Urschel, Stephanie; Sonntag, Stephan et al. (2008) The neuronal connexin36 interacts with and is phosphorylated by CaMKII in a way similar to CaMKII interaction with glutamate receptors. Proc Natl Acad Sci U S A 105:20964-9 |
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| Iacobas, Dumitru A; Iacobas, Sanda; Spray, David C (2007) Connexin43 and the brain transcriptome of newborn mice. Genomics 89:113-23 |
| Iacobas, Dumitru A; Iacobas, Sanda; Spray, David C (2007) Connexin-dependent transcellular transcriptomic networks in mouse brain. Prog Biophys Mol Biol 94:169-85 |
| Bai, Donglin; del Corsso, Cristiane; Srinivas, Miduturu et al. (2006) Block of specific gap junction channel subtypes by 2-aminoethoxydiphenyl borate (2-APB). J Pharmacol Exp Ther 319:1452-8 |
| Skeberdis, V Arvydas; Chevaleyre, Vivien; Lau, C Geoffrey et al. (2006) Protein kinase A regulates calcium permeability of NMDA receptors. Nat Neurosci 9:501-10 |
| Cusato, K; Ripps, H; Zakevicius, J et al. (2006) Gap junctions remain open during cytochrome c-induced cell death: relationship of conductance to 'bystander' cell killing. Cell Death Differ 13:1707-14 |
| Iacobas, Dumitru A; Iacobas, Sanda; Urban-Maldonado, Marcia et al. (2005) Sensitivity of the brain transcriptome to connexin ablation. Biochim Biophys Acta 1711:183-96 |
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