Molecular domains determining gap junction channel properties

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Gap junction channels are specialized membrane pore structures between cells, allowing ions and small signalling molecules in one cell to pass on to the neighbour cells. The building blocks for gap junction channels are a group of transmembrane proteins called connexins (Cx). 20 different types of connexins are identified in rodents. Six identical connexins or different connexins form a cylinder-shaped half channel known as a hemichannel. Back-to-back linking of two hemichannels forms a complete gap junction channel. Communication through gap junction channels is essential for synchronized, coordinated cellular activities and exchanging small molecules between cells in tissues. The gap junction channel pore size, the switch control for opening/closing, and the chemical sensitivities are different depending on the connexin subtypes that organize the channel. This proposal aims to reveal which part of the connexin molecule is responsible for the distinct functional properties of the neuronal connexin, Cx36. We plan to engineer several parts of Cx36 into Cx50, an eye lens connexin, to form chimera proteins. These chimera proteins will be expressed into cells for functional test of gap junction channel properties. Further subdivision of positively identified parts will be used to track down the minimum amino acid residue(s) required to display unique functional properties. The proposed research will assist us in understanding the molecular mechanisms in the control of opening/closing of these important channels and the molecular determinants for the ability of the channel to conduct ions. A comprehensive knowledge of structure-function relationships for gap junction molecules in neurons is critical in understanding the functions of these channels in synchronized brain activities.