FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2113326963> ?p ?o ?g. }

• W2113326963 endingPage "120" @default.
• W2113326963 startingPage "116" @default.
• W2113326963 abstract "The mechanism underlying activation of Ca2+ release-activated Ca2+ channels, in response to depletion of intracellular Ca2+ stores, has generated much interest. Recently, it was shown that Stim forms the relay between the Ca2+ store and the plasma membrane, where it activates the ion-channel forming protein Orai. Here, Penna et al. show that Orai is a dimer at rest and a tetramer when activated by Stim, raising the interesting possibility that dimerization is the trigger for channel activation. Ca2+-release-activated Ca2+ (CRAC) channels underlie sustained Ca2+ signalling in lymphocytes and numerous other cells after Ca2+ liberation from the endoplasmic reticulum (ER). RNA interference screening approaches identified two proteins, Stim1,2 and Orai3,4,5, that together form the molecular basis for CRAC channel activity6,7. Stim senses depletion of the ER Ca2+ store and physically relays this information by translocating from the ER to junctions adjacent to the plasma membrane1,8,9, and Orai embodies the pore of the plasma membrane calcium channel10,11,12. A close interaction between Stim and Orai, identified by co-immunoprecipitation12 and by Förster resonance energy transfer13, is involved in the opening of the Ca2+ channel formed by Orai subunits. Most ion channels are multimers of pore-forming subunits surrounding a central channel, which are preassembled in the ER and transported in their final stoichiometry to the plasma membrane. Here we show, by biochemical analysis after cross-linking in cell lysates and intact cells and by using non-denaturing gel electrophoresis without cross-linking, that Orai is predominantly a dimer in the plasma membrane under resting conditions. Moreover, single-molecule imaging of green fluorescent protein (GFP)-tagged Orai expressed in Xenopus oocytes showed predominantly two-step photobleaching, again consistent with a dimeric basal state. In contrast, co-expression of GFP-tagged Orai with the carboxy terminus of Stim as a cytosolic protein to activate the Orai channel without inducing Ca2+ store depletion or clustering of Orai into punctae yielded mostly four-step photobleaching, consistent with a tetrameric stoichiometry of the active Orai channel. Interaction with the C terminus of Stim thus induces Orai dimers to dimerize, forming tetramers that constitute the Ca2+-selective pore. This represents a new mechanism in which assembly and activation of the functional ion channel are mediated by the same triggering molecule." @default.
• W2113326963 created "2016-06-24" @default.
• W2113326963 creator A5048409002 @default.
• W2113326963 creator A5056296835 @default.
• W2113326963 creator A5070448855 @default.
• W2113326963 creator A5076450793 @default.
• W2113326963 creator A5083058833 @default.
• W2113326963 creator A5084339107 @default.
• W2113326963 creator A5090558491 @default.
• W2113326963 date "2008-09-28" @default.
• W2113326963 modified "2023-10-16" @default.
• W2113326963 title "The CRAC channel consists of a tetramer formed by Stim-induced dimerization of Orai dimers" @default.
• W2113326963 cites W1500581977 @default.
• W2113326963 cites W1978593035 @default.
• W2113326963 cites W1979573280 @default.
• W2113326963 cites W1982014643 @default.
• W2113326963 cites W1986554781 @default.
• W2113326963 cites W2001917660 @default.
• W2113326963 cites W2002609528 @default.
• W2113326963 cites W2009707152 @default.
• W2113326963 cites W2017608945 @default.
• W2113326963 cites W2020708758 @default.
• W2113326963 cites W2027039293 @default.
• W2113326963 cites W2028649950 @default.
• W2113326963 cites W2029301182 @default.
• W2113326963 cites W2038096428 @default.
• W2113326963 cites W2040263569 @default.
• W2113326963 cites W2042342392 @default.
• W2113326963 cites W2055864348 @default.
• W2113326963 cites W2059742450 @default.
• W2113326963 cites W2059989081 @default.
• W2113326963 cites W2079071687 @default.
• W2113326963 cites W2089040449 @default.
• W2113326963 cites W2101586949 @default.
• W2113326963 cites W2107562200 @default.
• W2113326963 cites W2108183974 @default.
• W2113326963 cites W2118988881 @default.
• W2113326963 cites W2127920119 @default.
• W2113326963 cites W2146341872 @default.
• W2113326963 cites W2157189708 @default.
• W2113326963 cites W2158029606 @default.
• W2113326963 cites W2163789582 @default.
• W2113326963 cites W2282032634 @default.
• W2113326963 doi "https://doi.org/10.1038/nature07338" @default.
• W2113326963 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2597643" @default.
• W2113326963 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18820677" @default.
• W2113326963 hasPublicationYear "2008" @default.
• W2113326963 type Work @default.
• W2113326963 sameAs 2113326963 @default.
• W2113326963 citedByCount "364" @default.
• W2113326963 countsByYear W21133269632012 @default.
• W2113326963 countsByYear W21133269632013 @default.
• W2113326963 countsByYear W21133269632014 @default.
• W2113326963 countsByYear W21133269632015 @default.
• W2113326963 countsByYear W21133269632016 @default.
• W2113326963 countsByYear W21133269632017 @default.
• W2113326963 countsByYear W21133269632018 @default.
• W2113326963 countsByYear W21133269632019 @default.
• W2113326963 countsByYear W21133269632020 @default.
• W2113326963 countsByYear W21133269632021 @default.
• W2113326963 countsByYear W21133269632022 @default.
• W2113326963 countsByYear W21133269632023 @default.
• W2113326963 crossrefType "journal-article" @default.
• W2113326963 hasAuthorship W2113326963A5048409002 @default.
• W2113326963 hasAuthorship W2113326963A5056296835 @default.
• W2113326963 hasAuthorship W2113326963A5070448855 @default.
• W2113326963 hasAuthorship W2113326963A5076450793 @default.
• W2113326963 hasAuthorship W2113326963A5083058833 @default.
• W2113326963 hasAuthorship W2113326963A5084339107 @default.
• W2113326963 hasAuthorship W2113326963A5090558491 @default.
• W2113326963 hasBestOaLocation W21133269634 @default.
• W2113326963 hasConcept C12554922 @default.
• W2113326963 hasConcept C158617107 @default.
• W2113326963 hasConcept C162740809 @default.
• W2113326963 hasConcept C170493617 @default.
• W2113326963 hasConcept C178790620 @default.
• W2113326963 hasConcept C181199279 @default.
• W2113326963 hasConcept C185592680 @default.
• W2113326963 hasConcept C201571599 @default.
• W2113326963 hasConcept C2776610495 @default.
• W2113326963 hasConcept C2778886173 @default.
• W2113326963 hasConcept C2779546866 @default.
• W2113326963 hasConcept C41625074 @default.
• W2113326963 hasConcept C50254741 @default.
• W2113326963 hasConcept C55493867 @default.
• W2113326963 hasConcept C79879829 @default.
• W2113326963 hasConcept C86803240 @default.
• W2113326963 hasConcept C95444343 @default.
• W2113326963 hasConceptScore W2113326963C12554922 @default.
• W2113326963 hasConceptScore W2113326963C158617107 @default.
• W2113326963 hasConceptScore W2113326963C162740809 @default.
• W2113326963 hasConceptScore W2113326963C170493617 @default.
• W2113326963 hasConceptScore W2113326963C178790620 @default.
• W2113326963 hasConceptScore W2113326963C181199279 @default.
• W2113326963 hasConceptScore W2113326963C185592680 @default.
• W2113326963 hasConceptScore W2113326963C201571599 @default.
• W2113326963 hasConceptScore W2113326963C2776610495 @default.
• W2113326963 hasConceptScore W2113326963C2778886173 @default.

• next