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Functional Stoichiometry and Local Enrichment of Calmodulin Interacting with Ca2+ Channels
Masayuki X. Mori,Michael G. Erickson,David T. Yue*
Calmodulin (CaM) interactions with Ca2+ channels mediate bothCa2+ regulation of channels and local Ca2+ triggering of transcriptionfactors implicated in neuronal memory. Crucial to these functionsare the number of CaM molecules (CaMs) regulating each channel,and the number of CaMs privy to the local Ca2+ signal from eachchannel. To resolve these parameters, we fused L-type Ca2+ channelsto single CaM molecules. These chimeric molecules revealed thata single CaM directs L-type channel regulation. Similar fusionmolecules were used to estimate the local CaM concentrationnear Ca2+ channels. This estimate indicates marked enrichmentof local CaM, as if a "school" of nearby CaMs were poised toenhance the transduction of local Ca2+ entry into diverse signalingpathways.
Ca2+ Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
* To whom correspondence should be addressed. E-mail: dyue{at}bme.jhu.edu
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