TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6

摘要

Abstract Maintaining plasma calcium levels within a narrow range is of vital importance for many physiological functions. Therefore, calcium transport processes in the intestine, bone and kidney are tightly regulated to fine-tune the rate of absorption, storage and excretion. The TRPV5 and TRPV6 calcium channels are viewed as the gatekeepers of epithelial calcium transport. Several calciotropic hormones control the channels at the level of transcription, membrane expression, and function. Recent technological advances have provided the first near-atomic resolution structural models of several TRPV channels, allowing insight into their architecture. While this field is still in its infancy, it has increased our understanding of molecular channel regulation and holds great promise for future structure-function studies of these ion channels. This review will summarize the mechanisms that control the systemic calcium balance, as well as extrapolate structural views to the molecular functioning of TRPV5/6 channels in epithelial calcium transport. Highlights ? Calcium balance is maintained by the bone-kidney-parathyroid feedback system. ? The PTH-Vitamin D-FGF23 hormone axis is essential for the systemic control of plasma calcium levels. ? Technical advances in structural biology have made it possible to solve TRP channel structures to near-atomic resolution. ? Structure-function relation of TRPV5/6 is vital for molecular understanding of epithelial calcium transport processes. ]]>