Mechanism of local and global Ca2+ sensing by calmodulin in complex with a Ca2+ channel.
Abstract
Calmodulin (CaM) in complex with Ca(2+) channels constitutes a prototype for Ca(2+)
sensors that are intimately colocalized with Ca(2+) sources. The C-lobe of CaM senses
local, large Ca(2+) oscillations due to Ca(2+) influx from the host channel, and the
N-lobe senses global, albeit diminutive Ca(2+) changes arising from distant sources.
Though biologically essential, the mechanism underlying global Ca(2+) 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 Ca(2+) oscillations seen by the CaM/channel complex. We find that global selectivity
arises from rapid Ca(2+) release from CaM combined with greater affinity of the channel
for Ca(2+)-free versus Ca(2+)-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 Ca(2+) sources.
Type
Journal articleSubject
AnimalsCalcium
Calcium Channels
Calcium Channels, N-Type
Calcium Signaling
Calmodulin
Cell Line
Electrophysiology
Humans
Mutagenesis
Point Mutation
Protein Structure, Tertiary
Rats
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https://hdl.handle.net/10161/15556Published Version (Please cite this version)
10.1016/j.cell.2008.05.025Publication Info
Tadross, Michael R; Dick, Ivy E; & Yue, David T (2008). Mechanism of local and global Ca2+ sensing by calmodulin in complex with a Ca2+ channel.
Cell, 133(7). pp. 1228-1240. 10.1016/j.cell.2008.05.025. Retrieved from https://hdl.handle.net/10161/15556.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Michael Raphael Tadross
Assistant Professor of Biomedical Engineering
Dr. Tadross' lab develops technologies to rapidly deliver drugs to genetically defined
subsets of cells in the brain. By using these reagents in mouse models of neuropsychiatric
disease, his group is mapping how specific receptors on defined cells and synapses
in the brain give rise to diverse neural computations and behaviors. The approach
leverages drugs currently in use to treat human neuropsychiatric disease, facilitating
clinically relevant interpretation of the mapping effort.<

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