Examination of Transport ATPases in Models of Disease

[摘要] Transport ATPases make up a family comprised of six types of transporters responsible formoving molecules including but not limited to H+, Na+, K+, Ca2+, Mn2+, Cu2+ and even flipping phospholipids across membrane leaflets. These versatile pumps play a major role in setting the cell’s electrochemical gradient and many members arose during gene duplications from evolutionarily related isoforms. In this study we looked at the role of secretory pathway Ca2+/Mn2+- ATPases in colon cancer biology. Two isoforms exist in mammalian cells however mounting evidence suggests that they may not play a compensatory role. To determine if there is a distinct contribution of SPCA1 or SPCA2 to colon cancer growth we performed a simple growth assay. We found that both shSPCA1 and shSPCA2 reduced Caco-2 growth at day three due to elevations in apoptosis.In the second part of this study, the contribution of two isoforms of the proton pump, V- ATPase a, were examined in the context of Candida albicans infection. C. albicans thrives in the gut as a commensal but maintains the propensity to establish septicemia and may become fatal. We found that the vacuolar form of a (Vph1) was responsible for vacuolar acidification and zinc clearance. Vph1 mutation, but not secretory Stv1, diminished hyphae formation and failed to establish a systemic infection in mouse. We conclude that vacuolar acidification is critical in the establishment of infection by C. albicans.

[发布机构] Johns Hopkins University

[效力级别] Physiology

[关键词] N/A;Physiology