Functional stoichiometry and local enrichment of calmodulin interacting with Ca2+ channels.
Calmodulin (CaM) interactions with Ca2+ channels mediate both Ca2+ regulation of channels and local Ca2+ triggering of transcription factors implicated in neuronal memory. Crucial to these functions are the number of CaM molecules (CaMs) regulating each channel, and the number of CaMs privy to the local Ca2+ signal from each channel. To resolve these parameters, we fused L-type Ca2+ channels to single CaM molecules. These chimeric molecules revealed that a single CaM directs L-type channel regulation. Similar fusion molecules were used to estimate the local CaM concentration near Ca2+ channels. This estimate indicates marked enrichment of local CaM, as if a "school" of nearby CaMs were poised to enhance the transduction of local Ca2+ entry into diverse signaling pathways.
Mori
Masayuki X
MX
Ca2+ Signals Laboratory, Department of Biomedical Engineering , Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Erickson
Michael G
MG
Yue
David T
DT
D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008433:Mathematics; D009154:Mutation; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
D020746:Calcium Channels, L-Type; D002147:Calmodulin; D017362:Cyclic AMP Response Element-Binding Protein; C419385:L-type calcium channel alpha(1C); D010455:Peptides; D011993:Recombinant Fusion Proteins; C011080:polyglycine; D002118:Calcium