Plasma Membrane Ca2+-ATPase's (PMCA) participate in epithelial Ca2+ transport and intracellular Ca2+ signaling. The Pmca4 isoform is enriched in distal nephron isolates and decreased in mice lacking the epithelial Ca2+ channel, Trpv5. We therefore hypothesized that Pmca4 plays a significant role in transcellular Ca2+ flux and investigated the localization and regulation of Pmca4 in Ca2+-transporting epithelia. Using antibodies directed specifically against Pmca4, we found it expressed only in the smooth muscle layer of mouse and human intestine, while pan-specific Pmca antibodies detected Pmca1 in lateral membranes of enterocytes. In kidney, Pmca4 showed broad localization to the distal nephron. In mouse, expression was most abundant in segments coexpressing the epithelial Ca2+ channel, Trpv5. Significant, albeit lower expression, was also evident in the region encompassing the cortical thick ascending limbs, macula densa, and early distal tubules as well as smooth muscle layers surrounding renal vessels. In human kidney, a similar pattern of distribution was observed, with highest PMCA4 expression in NCC positive tubules. Electron microscopy demonstrated Pmca4 localization in distal nephron cells at both the basolateral membrane and intracellular perinuclear compartments, but not submembranous vesicles, suggesting rapid trafficking to the plasma membrane is unlikely to occur in vivo. Pmca4 expression was not altered by perturbations in Ca2+ balance, pointing to a housekeeping function of the pump in Ca2+ transporting epithelia. In conclusion, Pmca4 shows a divergent expression pattern in Ca2+ transporting epithelia, inferring diverse roles for this isoform not limited to transepithelial Ca2+ transport.
- Transcellular calcium transport
- Copyright © 2014, American Journal of Physiology - Renal Physiology