Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2013 May 03;28818:12680-91. doi: 10.1074/jbc.M113.460949.
Show Gene links
Show Anatomy links
Competitive and non-competitive regulation of calcium-dependent inactivation in CaV1.2 L-type Ca2+ channels by calmodulin and Ca2+-binding protein 1.
Oz S
,
Benmocha A
,
Sasson Y
,
Sachyani D
,
Almagor L
,
Lee A
,
Hirsch JA
,
Dascal N
.
???displayArticle.abstract??? CaV1.2 interacts with the Ca(2+) sensor proteins, calmodulin (CaM) and calcium-binding protein 1 (CaBP1), via multiple, partially overlapping sites in the main subunit of CaV1.2, α1C. Ca(2+)/CaM mediates a negative feedback regulation of Cav1.2 by incoming Ca(2+) ions (Ca(2+)-dependent inactivation (CDI)). CaBP1 eliminates this action of CaM through a poorly understood mechanism. We examined the hypothesis that CaBP1 acts by competing with CaM for common interaction sites in the α1C- subunit using Förster resonance energy transfer (FRET) and recording of Cav1.2 currents in Xenopus oocytes. FRET detected interactions between fluorescently labeled CaM or CaBP1 with the membrane-attached proximal C terminus (pCT) and the N terminus (NT) of α1C. However, mutual overexpression of CaM and CaBP1 proved inadequate to quantitatively assess competition between these proteins for α1C. Therefore, we utilized titrated injection of purified CaM and CaBP1 to analyze their mutual effects. CaM reduced FRET between CaBP1 and pCT, but not NT, suggesting competition between CaBP1 and CaM for pCT only. Titrated injection of CaBP1 and CaM altered the kinetics of CDI, allowing analysis of their opposite regulation of CaV1.2. The CaBP1-induced slowing of CDI was largely eliminated by CaM, corroborating a competition mechanism, but 15-20% of the effect of CaBP1 was CaM-resistant. Both components of CaBP1 action were present in a truncated α1C where N-terminal CaM- and CaBP1-binding sites have been deleted, suggesting that the NT is not essential for the functional effects of CaBP1. We propose that CaBP1 acts via interaction(s) with the pCT and possibly additional sites in α1C.
Almagor,
The role of a voltage-dependent Ca2+ channel intracellular linker: a structure-function analysis.
2012, Pubmed,
Xenbase
Almagor,
The role of a voltage-dependent Ca2+ channel intracellular linker: a structure-function analysis.
2012,
Pubmed
,
Xenbase
Benmocha,
Characterization of the calmodulin-binding site in the N terminus of CaV1.2.
2009,
Pubmed
,
Xenbase
Berlin,
G alpha(i) and G betagamma jointly regulate the conformations of a G betagamma effector, the neuronal G protein-activated K+ channel (GIRK).
2010,
Pubmed
,
Xenbase
Berlin,
Two distinct aspects of coupling between Gα(i) protein and G protein-activated K+ channel (GIRK) revealed by fluorescently labeled Gα(i3) protein subunits.
2011,
Pubmed
,
Xenbase
Catterall,
Structure and regulation of voltage-gated Ca2+ channels.
2000,
Pubmed
Cens,
Voltage and calcium use the same molecular determinants to inactivate calcium channels.
1999,
Pubmed
Christel,
Ca2+-dependent modulation of voltage-gated Ca2+ channels.
2012,
Pubmed
Dai,
Supramolecular assemblies and localized regulation of voltage-gated ion channels.
2009,
Pubmed
DeMaria,
Calmodulin bifurcates the local Ca2+ signal that modulates P/Q-type Ca2+ channels.
2001,
Pubmed
Dick,
A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels.
2008,
Pubmed
Erickson,
FRET two-hybrid mapping reveals function and location of L-type Ca2+ channel CaM preassociation.
2003,
Pubmed
Fallon,
Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Ca(v)1.2 calcium channel.
2005,
Pubmed
Fallon,
Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca2+* calmodulins.
2009,
Pubmed
Few,
Differential regulation of CaV2.1 channels by calcium-binding protein 1 and visinin-like protein-2 requires N-terminal myristoylation.
2005,
Pubmed
Findeisen,
Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation.
2010,
Pubmed
Fowler,
Complex modulation of L-type Ca(2+) current inactivation by sorcin in isolated rabbit cardiomyocytes.
2009,
Pubmed
Haeseleer,
Five members of a novel Ca(2+)-binding protein (CABP) subfamily with similarity to calmodulin.
2000,
Pubmed
Halling,
Regulation of voltage-gated Ca2+ channels by calmodulin.
2006,
Pubmed
Halling,
Determinants in CaV1 channels that regulate the Ca2+ sensitivity of bound calmodulin.
2009,
Pubmed
Hayashi,
An expression system of rat calmodulin using T7 phage promoter in Escherichia coli.
1998,
Pubmed
Haynes,
Evolution and functional diversity of the Calcium Binding Proteins (CaBPs).
2012,
Pubmed
Hering,
Ca2+ channel block and inactivation: common molecular determinants.
1998,
Pubmed
Ivanina,
Modulation of L-type Ca2+ channels by gbeta gamma and calmodulin via interactions with N and C termini of alpha 1C.
2000,
Pubmed
James,
A rigorous experimental framework for detecting protein oligomerization using bioluminescence resonance energy transfer.
2006,
Pubmed
Kim,
Identification of the components controlling inactivation of voltage-gated Ca2+ channels.
2004,
Pubmed
,
Xenbase
Kim,
Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.
2010,
Pubmed
,
Xenbase
Lautermilch,
Modulation of CaV2.1 channels by the neuronal calcium-binding protein visinin-like protein-2.
2005,
Pubmed
Lee,
Ca2+/calmodulin binds to and modulates P/Q-type calcium channels.
1999,
Pubmed
Lee,
Molecular determinants of Ca(2+)/calmodulin-dependent regulation of Ca(v)2.1 channels.
2003,
Pubmed
Lee,
Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1.
2002,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Minor,
Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.
2010,
Pubmed
Mori,
Crystal structure of the CaV2 IQ domain in complex with Ca2+/calmodulin: high-resolution mechanistic implications for channel regulation by Ca2+.
2008,
Pubmed
Mori,
Functional stoichiometry and local enrichment of calmodulin interacting with Ca2+ channels.
2004,
Pubmed
Mouton,
Interactions of calmodulin with two peptides derived from the c-terminal cytoplasmic domain of the Ca(v)1.2 Ca2+ channel provide evidence for a molecular switch involved in Ca2+-induced inactivation.
2001,
Pubmed
Oz,
CaBP1 regulates voltage-dependent inactivation and activation of Ca(V)1.2 (L-type) calcium channels.
2011,
Pubmed
,
Xenbase
Park,
Nuclear magnetic resonance structure of calcium-binding protein 1 in a Ca(2+) -bound closed state: implications for target recognition.
2011,
Pubmed
Pate,
Determinants for calmodulin binding on voltage-dependent Ca2+ channels.
2000,
Pubmed
Patton,
A peptide segment critical for sodium channel inactivation functions as an inactivation gate in a potassium channel.
1993,
Pubmed
Pellman,
An N-terminal peptide from p60src can direct myristylation and plasma membrane localization when fused to heterologous proteins.
,
Pubmed
Peterson,
Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels.
1999,
Pubmed
Peterson,
Critical determinants of Ca(2+)-dependent inactivation within an EF-hand motif of L-type Ca(2+) channels.
2000,
Pubmed
Philips,
Compartmentalized signalling of Ras.
2005,
Pubmed
Pitt,
Molecular basis of calmodulin tethering and Ca2+-dependent inactivation of L-type Ca2+ channels.
2001,
Pubmed
,
Xenbase
Qin,
Ca2+-induced inhibition of the cardiac Ca2+ channel depends on calmodulin.
1999,
Pubmed
,
Xenbase
Richter,
Differential capacity for translation and lack of competition between mRNAs that segregate to free and membrane-bound polysomes.
1981,
Pubmed
,
Xenbase
Rieke,
Characterization of Ca2+-binding protein 5 knockout mouse retina.
2008,
Pubmed
Romanin,
Ca(2+) sensors of L-type Ca(2+) channel.
2000,
Pubmed
Sanabria,
Spatial diffusivity and availability of intracellular calmodulin.
2008,
Pubmed
Schrauwen,
A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment.
2012,
Pubmed
Shaltiel,
Complex regulation of voltage-dependent activation and inactivation properties of retinal voltage-gated Cav1.4 L-type Ca2+ channels by Ca2+-binding protein 4 (CaBP4).
2012,
Pubmed
Soldatov,
Ca2+ channel moving tail: link between Ca2+-induced inactivation and Ca2+ signal transduction.
2003,
Pubmed
Soldatov,
Molecular structures involved in L-type calcium channel inactivation. Role of the carboxyl-terminal region encoded by exons 40-42 in alpha1C subunit in the kinetics and Ca2+ dependence of inactivation.
1997,
Pubmed
,
Xenbase
Tadross,
Molecular endpoints of Ca2+/calmodulin- and voltage-dependent inactivation of Ca(v)1.3 channels.
2010,
Pubmed
Tadross,
Mechanism of local and global Ca2+ sensing by calmodulin in complex with a Ca2+ channel.
2008,
Pubmed
Takanishi,
GFP-based FRET analysis in live cells.
2006,
Pubmed
Tang,
Apocalmodulin and Ca2+ calmodulin-binding sites on the CaV1.2 channel.
2003,
Pubmed
Thomsen,
Accessory subunit KChIP2 modulates the cardiac L-type calcium current.
2009,
Pubmed
Tippens,
Caldendrin, a neuron-specific modulator of Cav/1.2 (L-type) Ca2+ channels.
2007,
Pubmed
Van Petegem,
Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-Ca2+/calmodulin complex.
2005,
Pubmed
Walker,
Subunit interaction sites in voltage-dependent Ca2+ channels: role in channel function.
1998,
Pubmed
Weiss,
The Hill equation revisited: uses and misuses.
1997,
Pubmed
Wingard,
Structural analysis of Mg2+ and Ca2+ binding to CaBP1, a neuron-specific regulator of calcium channels.
2005,
Pubmed
Xia,
Mechanism of calcium gating in small-conductance calcium-activated potassium channels.
1998,
Pubmed
,
Xenbase
Zheng,
Spectroscopy-based quantitative fluorescence resonance energy transfer analysis.
2006,
Pubmed
,
Xenbase
Zheng,
Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels.
2004,
Pubmed
,
Xenbase
Zhou,
Molecular mechanism for divergent regulation of Cav1.2 Ca2+ channels by calmodulin and Ca2+-binding protein-1.
2005,
Pubmed
Zhou,
Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with Cav1.2 (L-type) Ca2+ channels.
2004,
Pubmed
Zühlke,
Ca2+-sensitive inactivation and facilitation of L-type Ca2+ channels both depend on specific amino acid residues in a consensus calmodulin-binding motif in the(alpha)1C subunit.
2000,
Pubmed
Zühlke,
Calmodulin supports both inactivation and facilitation of L-type calcium channels.
1999,
Pubmed
,
Xenbase
