Cohesion of epithelial ion homeostasis: implementing calcium transport with sodium transporters?

Abstract

THE ABILITY TO MOVE SOLUTES between the exterior and interior of an organism, between different extracellular compartments, between intracellular and extracellular space, and between organelles and cytoplasm involves a myriad of transport mechanisms; all of which are indispensible for life. Considering the wide variety of solutes that have to be translocated at each of these levels, the precise transport machineries devoted to each solute, and the host of regulatory mechanisms accompanying each of these ensembles, one ponders whether we have enough genes in our genome to achieve these homeostatic feats. The intuitive answer is of course “yes” since we have already succeeded in doing so. While the utilization of multiple proteins to serve the same means bestows redundancy and insurance, the evolution of one protein to execute multiple functions maximizes genetic economy. The fact that one gene product can serve multiple and diverse functions may be a well-known and foregone conclusion to all but is still a remarkable phenomenon to be marveled. Take as an example the most abundant protein in our circulation: hemoglobin. In addition to its known function of carrying O2, hemoglobin also regulates O2 offloading as a metabolic sensor of tissue oxygenation, couples CO2 and nitric oxide transport at the lung and periphery, buffers H, releases vasodilators to directly regulate local blood flow, regulates circadian rhythm of antioxidant, and may even participates in immune surveillance. It is unlikely that this multitasking coevolved completely contemporaneously but was more likely to have done so in tandem, or more likely in “overlapping tandems,” where the needs of one function modulate the evolution of the others. Inherent in this system of serving many masters exist inevitable conflicts that at some point mandate some degree of compromise.