Molecular Mechanism for Divergent Regulation of Cav1.2 Ca2+ Channels by Calmodulin and Ca2+-binding Protein-1

Zhou, Hong; Yu, Kuai; McCoy, Kelly L.; Lee, Amy

doi:10.1074/jbc.m504167200

Cited by 96 publications

(151 citation statements)

References 44 publications

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“…In addition, in the mouse, deletion of another component of the Cav1.4 channel complex, the auxiliary ␤ 2a subunit, also leads to CSNB2-like phenotype (10). Recently, it has been shown that mutations in the gene coding for CaBP4 are also associated with CSNB2 and other closely related nonstationary retinal diseases in humans (11)(12)(13)(14). In line with these findings, deletion of CaBP4 in the mouse leads to a CSNB2-like phenotype (15).…”

Section: Cav14 L-type Camentioning

confidence: 79%

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)

Shaltiel

Paparizos

Fenske

et al. 2012

Journal of Biological Chemistry

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Section: Cav14 L-type Camentioning

confidence: 79%

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)

Shaltiel

Paparizos

Fenske

et al. 2012

Journal of Biological Chemistry

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“…Splice variants 9 and 26 have the following substitution: 1618 LRIKTEGNLEQANE-ELR A IIKKIWKRTSMKLLDQVVPPAGDDEVTVGKF-YATFLIQEYFRKFKKRKEQGLVGKPSQRNALSL 1699 3 LRETELSSQVQYQAKEASLLERRRKSSHPKSSTKPNK-LLSSGGSTGWVEDARALEGQVLARGCGWLGSLEER-ERGPHHPPLGF. In isoforms 10,13,14,15,24,25,27 and 29, the glutamic residue 1623 is replaced with the sequence EEG-PSPSEAHQGAEDPFRPA. In all of these splice variants, the coiled-coil interaction is expected to be totally disrupted (Fig.…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca ²⁺ ·calmodulins

Fallon

Baker

Xiong

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

103

125

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Voltage-dependent calcium channels (CaV) open in response to changes in membrane potential, but their activity is modulated by Ca 2؉ binding to calmodulin (CaM). Structural studies of this family of channels have focused on CaM bound to the IQ motif; however, the minimal differences between structures cannot adequately describe CaM's role in the regulation of these channels. We report a unique crystal structure of a 77-residue fragment of the Ca V1.2 ␣1 subunit carboxyl terminus, which includes a tandem of the pre-IQ and IQ domains, in complex with Ca 2؉ ⅐CaM in 2 distinct binding modes. The structure of the Ca V1.2 fragment is an unusual dimer of 2 coiled-coiled pre-IQ regions bridged by 2 Ca 2؉ ⅐CaMs interacting with the pre-IQ regions and a canonical Ca V1-IQ-Ca 2؉ ⅐CaM complex. Native Ca V1.2 channels are shown to be a mixture of monomers/dimers and a point mutation in the pre-IQ region predicted to abolish the coiled-coil structure significantly reduces Ca 2؉ -dependent inactivation of heterologously expressed CaV1.2 channels.structure ͉ function ͉ voltage-gated calcium channel E xcitation-contraction coupling and other important cellular processes are controlled by the voltage-gated Ca 2ϩ channels (Ca V ). The ubiquitous Ca 2ϩ sensor and regulator molecule, calmodulin, is an essential component of Ca V regulation by Ca 2ϩ , and several regions of the cytoplasmic carboxyl terminus of the Ca V ␣1 subunit have been identified as critical molecular determinants for CaM's regulation of Ca V . Ca 2ϩ ⅐CaM bound to the IQ motif of the carboxyl terminus of the ␣ 1 subunit of L-type Ca 2ϩ channels is required for both a feed-forward regulation, Ca 2ϩ -dependent facilitation (CDF), and a feed-back regulation, Ca 2ϩ -dependent inactivation (CDI) (1, 2). CaM acts as the Ca 2ϩ sensor for CDI in Ca V 1.2, Ca V 2.1, Ca V 2.2 and Ca V 2.3, and CDF in Ca V 1.2 and Ca V 2.1. This duality of Ca V regulation by CaM suggests that there are either multiple binding sites or alternative interactions exist to regulate the channel based on different functional states of the channel.Regions upstream of the IQ motif, designated the pre-IQ region, have been implicated in Ca 2ϩ ⅐CaM regulation of the channel (3-5). Consistent with this, 2 different segments within the pre-IQ motif (1606-1627 and 1618-1652, identified as the A and C sequences, respectively) have been shown to bind CaM (4). Moreover, both the IQ motif and amino acids within the pre-IQ region (N1630-E1631) have been indicated to be critical for Ca V 1.2 CDI (6).Recent crystal structures of CaM in complex with the IQ motifs from Ca V 1.2 (7, 8), Ca V 2.2 and Ca V 2.3 (5) reveal few structural differences that could account for the differences in regulation of Ca V 1.2 and Ca V 2.2 by CaM. However, very little is known about the structure of the pre-IQ region or the molecular basis for its interactions with CaM.Here, we report the isolation and determination of the crystal structure at 2.1 Å resolution of a 77-residue (1609-1685) fragment of the carboxyl terminus of the ␣ 1 ...

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“…Differential modulation of L-type channels depending on the splice isoform of CaBP1 has also been observed. CaBP1-Short has been shown to completely inhibit inactivation of Ca V 1.2 channels (Zhou et al 2005), but caldendrin causes a more modest suppression and signals through a different set of molecular determinants (Tippens and Lee 2007). This suggests that the subcellular localization of CaBP1 splice variants is important for their function and there are likely to be individual roles for each protein.…”

Section: Calcium Sensor Proteins In Neuronal Functionmentioning

confidence: 99%

“…For instance, both CaBP1 and calmodulin bind to L-type Ca 2þ channels with calmodulin causing Ca 2þ -induced channel closure but CaBP1 promoting channel opening (Zhou et al 2004a;Zhou et al 2005). Both calmodulin and CaBP1 also regulate inositol 1,4,5-trisphosphate receptors (IP 3 Rs) (Yang et al 2002;Haynes et al 2004;Kasri et al 2004) with CaBP1 binding the type I IP 3 R with 100-fold higher affinity than calmodulin.…”

Section: Calcium Sensor Proteins In Neuronal Functionmentioning

confidence: 99%

“…CaBP1-Long and -Short have been found to have roles in the regulation of various Ca 2þ -channels including P/ Q-type (Ca V 2.1) channels (Lee et al 2002), L-type (Ca V 1.2) channels (Zhou et al 2005;Cui et al 2007), TRPC5 channels (KinoshitaKawada et al 2005, and IP 3 Rs (Yang et al 2002), which they apparently inhibit Kasri et al 2004). The interaction of Ca V 2.1 with CaBP1 appears to rely acutely upon amino-terminal myristoylation.…”

Section: Calcium Sensor Proteins In Neuronal Functionmentioning

confidence: 99%

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The Diversity of Calcium Sensor Proteins in the Regulation of Neuronal Function

McCue

Haynes²,

Burgoyne

2010

Cold Spring Harbor Perspectives in Biology

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Molecular Mechanism for Divergent Regulation of Cav1.2 Ca2+ Channels by Calmodulin and Ca2+-binding Protein-1

Cited by 96 publications

References 44 publications

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)

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)

Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca ²⁺ ·calmodulins

The Diversity of Calcium Sensor Proteins in the Regulation of Neuronal Function

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Molecular Mechanism for Divergent Regulation of Cav1.2 Ca2+ Channels by Calmodulin and Ca2+-binding Protein-1

Cited by 96 publications

References 44 publications

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)

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)

Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca 2+ ·calmodulins

The Diversity of Calcium Sensor Proteins in the Regulation of Neuronal Function

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Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca ²⁺ ·calmodulins