Abstract
Ca2+ ions play a variety of roles in the human body as well as within a single cell. Cellular Ca2+ signal transduction processes are governed by Ca2+ sensing and Ca2+ transporting proteins. In this review, we discuss the Ca2+ and the Ca2+-sensing ion channels with particular focus on the structure-function relationship of the Ca2+ release-activated Ca2+ (CRAC) ion channel, the Ca2+-activated K+ (KCa2+) ion channels, and their modulation via other cellular components. Moreover, we highlight their roles in healthy signaling processes as well as in disease with a special focus on cancer. As KCa2+ channels are activated via elevations of intracellular Ca2+ levels, we summarize the current knowledge on the action mechanisms of the interplay of CRAC and KCa2+ ion channels and their role in cancer cell development.
Highlights
Ion channels form hydrophilic pores in the cell membrane and allow selective permeation of ions of appropriate size and charge across the membrane down their electrochemical gradient
We aim to focus on the structure/function relationship of Ca2+-activated potassium ion channels, as they have been reported to interplay with the calcium release-activated calcium (CRAC) channel
Clear evidence is emerging that an interplay of Ca2+ and KCa2+ ion channels is decisive in particular in the progression of cancer cell development and growth, as their downregulation reduces cancer cell proliferation and migration
Summary
Ion channels form hydrophilic pores in the cell membrane and allow selective permeation of ions of appropriate size and charge across the membrane down their electrochemical gradient. Alterations in the cellular Ca2+ levels are tightly controlled by a set of Ca2+ signaling proteins including Ca2+ transporters, Ca2+ regulated ion channels, Ca2+-binding proteins, Ca2+-storage proteins, and Ca2+-dependent effectors They act with highly spatiotemporal dynamics to govern the respective cellular processes in a cell-type-specific manner. This large variety of Ca2+ ion channels governs via highly specific Ca2+ signals a multitude of essential events in a cell’s life including gene expression, secretion, proliferation, differentiation, or migration They control a plethora of healthy processes such as muscle contraction, neuronal function, and immune cell function [20,21,55]. Between the N-terminal portion of the first SOAR monomer and the C-terminal portion of the second SOAR monomer
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