Mechanism of local and global Ca2+ sensing by calmodulin in complex with a Ca2+ channel.
dc.contributor.author | Tadross, Michael R | |
dc.contributor.author | Dick, Ivy E | |
dc.contributor.author | Yue, David T | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2017-09-19T16:09:30Z | |
dc.date.available | 2017-09-19T16:09:30Z | |
dc.date.issued | 2008-06-27 | |
dc.description.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. | |
dc.identifier | ||
dc.identifier | S0092-8674(08)00684-3 | |
dc.identifier.eissn | 1097-4172 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | Elsevier BV | |
dc.relation.ispartof | Cell | |
dc.relation.isversionof | 10.1016/j.cell.2008.05.025 | |
dc.subject | Animals | |
dc.subject | Calcium | |
dc.subject | Calcium Channels | |
dc.subject | Calcium Channels, N-Type | |
dc.subject | Calcium Signaling | |
dc.subject | Calmodulin | |
dc.subject | Cell Line | |
dc.subject | Electrophysiology | |
dc.subject | Humans | |
dc.subject | Mutagenesis | |
dc.subject | Point Mutation | |
dc.subject | Protein Structure, Tertiary | |
dc.subject | Rats | |
dc.title | Mechanism of local and global Ca2+ sensing by calmodulin in complex with a Ca2+ channel. | |
dc.type | Journal article | |
duke.contributor.orcid | Tadross, Michael R|0000-0002-7752-6380 | |
pubs.author-url | ||
pubs.begin-page | 1228 | |
pubs.end-page | 1240 | |
pubs.issue | 7 | |
pubs.organisational-group | Biomedical Engineering | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Pratt School of Engineering | |
pubs.publication-status | Published | |
pubs.volume | 133 |
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