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

Tadross, Michael R

Dick, Ivy E

Yue, David T

United States

2017-09-19T16:09:30Z

2017-09-19T16:09:30Z

2008-06-27

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.

https://www.ncbi.nlm.nih.gov/pubmed/18585356

S0092-8674(08)00684-3

1097-4172

https://hdl.handle.net/10161/15556

eng

Elsevier BV

Cell

10.1016/j.cell.2008.05.025

Animals

Calcium

Calcium Channels

Calcium Channels, N-Type

Calcium Signaling

Calmodulin

Cell Line

Electrophysiology

Humans

Mutagenesis

Point Mutation

Protein Structure, Tertiary

Rats

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

Journal article

Tadross, Michael R|0000-0002-7752-6380

https://www.ncbi.nlm.nih.gov/pubmed/18585356

1228

1240

7

Biomedical Engineering

Duke

Pratt School of Engineering

Published

133