期刊
CELL
卷 133, 期 7, 页码 1228-1240出版社
CELL PRESS
DOI: 10.1016/j.cell.2008.05.025
关键词
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资金
- NHLBI NIH HHS [R37 HL076795] Funding Source: Medline
- NIDCD NIH HHS [P30 DC005211, T32 DC000023] Funding Source: Medline
- NIMH NIH HHS [R01 MH065531] Funding Source: Medline
Calmodulin (CaM) in complex with Ca2+ channels constitutes a prototype for Ca2+ sensors that are intimately colocalized with Ca2+ sources. The C-lobe of CaM senses local, large Ca2+ oscillations due to Ca2+ influx from the host channel, and the N-lobe senses global, albeit diminutive Ca2+ changes arising from distant sources. Though biologically essential, the mechanism underlying global Ca2+ sensing has remained unknown. Here, we advance a theory of how global selectivity arises, and we experimentally validate this proposal with methodologies enabling millisecond control of Ca2+ oscillations seen by the CaM/channel complex. We find that global selectivity arises from rapid Ca2+ release from CaM combined with greater affinity of the channel for Ca2+-free versus Ca2+-bound CaM. The emergence of complex decoding properties from the juxtaposition of common elements, and the techniques developed herein, promise generalization to numerous molecules residing near Ca2+ sources.
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