Mechanism of local and global Ca2+ sensing by calmodulin in complex with a Ca2+ channel.

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2008-06-27

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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.

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10.1016/j.cell.2008.05.025

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Tadross, Michael R, Ivy E Dick and David T Yue (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.

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Scholars@Duke

Tadross

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.

He received his B.S. degree in Electrical & Computer Engineering at Rutgers University, an M.D.-Ph.D. degree in Biomedical Engineering at the Johns Hopkins School of Medicine, and completed his postdoctoral study in Cellular Neuroscience at Stanford University. He began his independent research program as a fellow at the HHMI Janelia Research Campus.


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