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AuthorSmith, Holly A.
AuthorThillaiappan, Nagendra Babu
AuthorRossi, Ana M.
Available date2023-11-19T05:45:32Z
Publication Date2023
Publication NameCell Calcium
ResourceScopus
ISSN1434160
URIhttp://dx.doi.org/10.1016/j.ceca.2023.102761
URIhttp://hdl.handle.net/10576/49414
AbstractInositol 1,4,5-trisphosphate receptors (IP3Rs) are large tetrameric channels which sit mostly in the membrane of the endoplasmic reticulum (ER) and mediate Ca2+ release from intracellular stores in response to extracellular stimuli in almost all cells. Dual regulation of IP3Rs by IP3 and Ca2+ itself, upstream "licensing", and the arrangement of IP3Rs into small clusters in the ER membrane, allow IP3Rs to generate spatially and temporally diverse Ca2+ signals. The characteristic biphasic regulation of IP3Rs by cytosolic Ca2+ concentration underpins regenerative Ca2+ signals by Ca2+-induced Ca2+-release, while also preventing uncontrolled explosive Ca2+ release. In this way, cells can harness a simple ion such as Ca2+ as a near-universal intracellular messenger to regulate diverse cellular functions, including those with conflicting outcomes such as cell survival and cell death. High-resolution structures of the IP3R bound to IP3 and Ca2+ in different combinations have together started to unravel the workings of this giant channel. Here we discuss, in the context of recently published structures, how the tight regulation of IP3Rs and their cellular geography lead to generation of "elementary" local Ca2+ signals known as Ca2+ "puffs", which form the fundamental bottleneck through which all IP3-mediated cytosolic Ca2+ signals must first pass.
SponsorThis work was supported by the Medical Research Council ( MR/T028378/1 to A.M. Rossi and G. Ladds) and the Biotechnology and Biological Sciences Research Council ( BB/ T012986/1 to G. Ladds). H. A. Smith is supported by an iCASE award from Cairn Research and the Biotechnology and Biological Sciences Research Council . We thank Martin Bootman and David Prole for insightful discussions. A.M. Rossi is a fellow of Queens' College, Cambridge.
Languageen
PublisherElsevier
SubjectCa2+ puffs
Ca2+ signals
Cryo-EM structures
Inositol 1,4,5-trisphosphate receptors
KRas-induced actin-interacting protein (KRAP)
TitleIP3 receptors: An "elementary" journey from structure to signals
TypeArticle
Volume Number113
dc.accessType Abstract Only


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