RGD Reference Report - Caldendrin, a neuron-specific modulator of Cav/1.2 (L-type) Ca2+ channels. - Rat Genome Database

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Caldendrin, a neuron-specific modulator of Cav/1.2 (L-type) Ca2+ channels.

Authors: Tippens, AL  Lee, A 
Citation: Tippens AL and Lee A, J Biol Chem. 2007 Mar 16;282(11):8464-73. Epub 2007 Jan 15.
RGD ID: 7207146
Pubmed: PMID:17224447   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M611384200   (Journal Full-text)

EF-hand Ca2+-binding proteins such as calmodulin and CaBP1 have emerged as important regulatory subunits of voltage-gated Ca2+ channels. Here, we show that caldendrin, a variant of CaBP1 enriched in the brain, interacts with and distinctly modulates Cav1.2 (L-type) voltage-gated Ca2+ channels relative to other Ca2+-binding proteins. Caldendrin binds to the C-terminal IQ-domain of the pore-forming alpha1-subunit of Cav1.2 (alpha(1)1.2) and competitively displaces calmodulin and CaBP1 from this site. Compared with CaBP1, caldendrin causes a more modest suppression of Ca2+-dependent inactivation of Cav1.2 through a different subset of molecular determinants. Caldendrin does not bind to the N-terminal domain of alpha11.2, a site that is critical for functional interactions of the channel with CaBP1. Deletion of the N-terminal domain inhibits CaBP1, but spares caldendrin modulation of Cav1.2 inactivation. In contrast, mutations of the IQ-domain abolish physical and functional interactions of caldendrin and Cav1.2, but do not prevent channel modulation by CaBP1. Using antibodies specific for caldendrin and Cav1.2, we show that caldendrin coimmunoprecipitates with Cav1.2 from the brain and colocalizes with Cav1.2 in somatodendritic puncta of cortical neurons in culture. Our findings reveal functional diversity within related Ca2+-binding proteins, which may enhance the specificity of Ca2+ signaling by Cav1.2 channels in different cellular contexts.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of voltage-gated calcium channel activity  IDA 7207146 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dendrite  IDA 7207146; 7207146 RGD 
neuronal cell body  IDA 7207146; 7207146 RGD 
protein-containing complex  IDA 7207146; 7207146 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Cabp1  (calcium binding protein 1)
Cacna1c  (calcium voltage-gated channel subunit alpha1 C)


Additional Information