title: Pore opening mechanism of CRAC channels.
abstract: Three decades ago, James W. Putney Jr. conceptualized the idea of store-operated calcium entry (SOCE) to explain how depletion of endoplasmic reticulum (ER) Ca2+stores evokes Ca2+influx across the plasma membrane. Since the publication of this highly influential idea, it is now established that SOCE is universal among non-excitable and probably even many types of excitable cells, and contributes to numerous effector functions impacting immunity, muscle contraction, and brain function. The molecules encoding SOCE, the STIM and Orai proteins, are now known and our understanding of how this pathway is activated in response to ER Ca2+store depletion has advanced significantly. In this review, we summarize the current knowledge of how Orai1 channels are activated by STIM1, focusing on recent work supporting a hydrophobic gating mechanism for the opening of the Orai1 channel pore.
authors.affiliation: Department of Pharmacology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, United States.
authors.forename: Priscilla S-W
authors.initials: PS
authors.lastname: Yeung
authors.affiliation: Department of Pharmacology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, United States.
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Department of Pharmacology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, United States. Electronic address: m-prakriya@northwestern.edu.
authors.forename: Murali
authors.initials: M
authors.lastname: Prakriya
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000071739:Calcium Release Activated Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans
chemical_list: D000071739:Calcium Release Activated Calcium Channels; D002118:Calcium
keywords: CRAC channel; Calcium; Orai1; SOCE; STIM1