Molecular Choreography and Structure of Ca²⁺ Release-Activated Ca²⁺ (CRAC) and K_Ca2+ Channels and Their Relevance in Disease with Special Focus on Cancer

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.

Keywords

• STIM1
• Orai1
• CRAC channels
• store-operated channel activation (SOCE), Ca²⁺-activated K⁺ channels (K_Ca2+), SK3
• SK3-Orai1 interplay