Abstract
Potassium-dependent sodium-calcium exchangers (NCKX) have emerged as key determinants of calcium (Ca2+) signaling and homeostasis, especially in environments where ion concentrations undergo large changes, such as excitatory cells and transport epithelia. The regulation of NCKX transporters enables them to respond to the changing cellular environment thereby helping to shape the extent and kinetics of Ca2+ signals. This review examines the current knowledge of the different ways in which NCKX activity can be modulated. These include (i) cellular and dynamic subcellular location (ii); changes in protein expression mediated at the gene, transcript, or protein level (iii); genetic changes resulting in altered protein structure or expression (iv); regulation via changes in substrate concentration (v); and post-translational modification, partner protein interactions, and allosteric regulation. Detailed mechanistic understanding of NCKX regulation is an emerging area of research with the potential to provide important new insights into transporter function, the control of Ca2+ signals, and possible interventions for dysregulated Ca2+ homeostasis.
Funder
National Science and Engineering Research Council of Canada
Libin Cardiovascular Institute at the University of Calgary
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference145 articles.
1. Calcium signalling: Dynamics, homeostasis and remodelling;Berridge;Nat. Rev. Mol. Cell Biol.,2003
2. Calcium signalling remodelling and disease;Berridge;Biochem. Soc. Trans.,2012
3. Fundamentals of Cellular Calcium Signaling: A Primer;Bootman;Cold Spring Harb. Perspect. Biol.,2020
4. Calcium Signaling Mechanisms Across Kingdoms;Luan;Annu. Rev. Cell Dev. Biol.,2021
5. Pallafacchina, G., Zanin, S., and Rizzuto, R. (2021). From the Identification to the Dissection of the Physiological Role of the Mitochondrial Calcium Uniporter: An Ongoing Story. Biomolecules, 11.
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献