Channel-Transporter Correlation

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Structural and functional correlations of channels and/or transporters were investigated from physiological, molecular biological and biochemical points of view. During these three years in this study, new channels (over 29) and new transporters (over 42) were discovered, and their genes were cloned. Structure-function correlations were elucidated by identification of numbers of functional domains and amino acid sites. New types of functional or structural correlation between channels and transporters were also demonstrated (over 10). New diseases were identified to be due to mutations of genes of channels or transporters (over 10). Especially a big progress was achieved in the research of ATP-binding cassette (ABC) transporter proteins. For example, a novel ABC protein cMOAT was cloned and found to mediate the ATP-dependent transport of glutathion-conjugates. The expression of cMOAT was found to be defective in the Dubin-Johnson syndrome. The ATP-sensitive KィイD1+ィエD1 channel was revealed to be a complex of two subunits : SUR1 of the ABC protein family and Kir6.2 of the inward-rectifier KィイD1+ィエD1 channel family. Some of ABC proteins have been found to have more than one activities of transporter, channel and their regulator. For example, P-glycoprotein and CFTR were found to be a regulator for volume-sensitive ClィイD1-ィエD1 channel and ATP release, respectively.