西亚试剂：Mechanism of Local and Global Ca2+ Sensing by Calmodulin in

Mechanism of Local and Global Ca2+ Sensing by Calmodulin in Complex with a Ca2+ Channel
Michael R. Tadross,1 Ivy E. Dick,1 and David T. Yue1,

1 Calcium Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, Ross Building, Room 713, 720 Rutland Avenue, Baltimore, MD 21205, USA

Summary
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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