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Functional diversification of sea urchin ABCC1 (MRP1) by alternative splicing


The results of this study extend and validate the heterologous expression approach we have adapted for analysis of sea urchin ABC transporters. These assays are important, because they reveal the transporters that could be responsible for observed activities and fingerprint the relevant suspects for analysis by more laborious immunochemical methods. Large overexpression has been used to ensure that the vast majority of the observed efflux activity comes from the recombinant protein, which is essential for characterization of substrate selectivity.

Here, we showed that for localization studies the protein can be reproducibly titrated to levels that increase corresponding transport activity only twofold and still be functionally imaged by routine confocal microscopy (Fig. 4B), albeit with use of high-sensitivity detectors. More importantly, these experiments indicated that localization of both forms of sea urchin ABCC1 could be both apical and bilateral, depending on developmental stage and independent of expression level. This dual location could be an additional mechanism for diversification of function in both protection and signaling.

Finally, an important step was to demonstrate the expression of functional human MRP1. An interesting observation was that while sea urchin protein exhibited both apical and basolateral efflux activity, the human protein only appeared to act at the basolateral membrane, possibly indicating that the differences in localization of sea urchin and human proteins are likely to be inherent features of the transporters themselves. Collectively, the results indicate that the sea urchin is an important system in which to understand the evolution of MRP proteins.

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