2002
DOI: 10.1074/jbc.m206763200
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Lobe-dependent Regulation of Ryanodine Receptor Type 1 by Calmodulin

Abstract: Calmodulin activates the skeletal muscle Ca 2؉ release channel RYR1 at nM Ca 2؉ concentrations and inhibits the channel at M Ca 2؉ concentrations. Using a deletion mutant of calmodulin, we demonstrate that amino acids 2-8 are required for high affinity binding of calmodulin to RYR1 at both nM and M Ca 2؉ concentrations and are required for maximum inhibition of the channel at M Ca 2؉ concentrations. In contrast, the addition of three amino acids to the N terminus of calmodulin increased the affinity for RYR1 a… Show more

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Cited by 67 publications
(87 citation statements)
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References 33 publications
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“…The N-lobe of CaM is more loosely bound to RyRp C-terminal region in the absence of Ca 2þ , while the C-lobe binding to RyRp N-terminal is unaffected by Ca 2þ . Consistent with our results, Xiong et al (44) showed that a truncated CaM representing the N-lobe (amino acids 1-79) (Fig. 5).…”
Section: Discussionsupporting
confidence: 93%
“…The N-lobe of CaM is more loosely bound to RyRp C-terminal region in the absence of Ca 2þ , while the C-lobe binding to RyRp N-terminal is unaffected by Ca 2þ . Consistent with our results, Xiong et al (44) showed that a truncated CaM representing the N-lobe (amino acids 1-79) (Fig. 5).…”
Section: Discussionsupporting
confidence: 93%
“…2-4). The ryanodine receptor can also bind apoCaM, but in contrast to NR1 C0 it appears that the N-and C-domains of CaM are associated with different regions of the ryanodine receptor under Ca 2ϩ -depleted and Ca 2ϩ -saturating conditions (43) and that Ca 2ϩ binding shifts the conformation of CaM rather than causing the N-domain to associate per se (26,44).…”
Section: Resultsmentioning
confidence: 97%
“…Pre-association of apoCaM with ion channels via the C-domain has been studied at a biochemical level in only a couple of other cases, including SK channels (41) and ryanodine receptors (26). However, the NMDA receptor likely has a CaM domain-specific molecular mechanism of regulation different from those channels.…”
Section: Resultsmentioning
confidence: 99%
“…To test this possibility we made use of the dominant negative CaM ((Nϩ3)CaM). Previous studies have demonstrated that (Nϩ3)CaM binds to isolated RyR1 with ϳ5-fold higher affinity than wild type CaM, binds R3614 -3643 similar to wild type CaM, prevents the localization of fluorescently labeled wild type CaM (Alexa488-CaM) in permeabilized muscle fibers, and prevents the increase in spark frequency due to exogenous wild type CaM in permeabilized muscle fibers, but it does not itself increase the activation rate of RyR (9,22). Fig.…”
Section: The Effects Of R3614 -3643 and Recombinant Cam On Ca 2ϩmentioning
confidence: 90%