| AKAP79 modulation of L-type channels involves disruption of intramolecular interactions in the CaV1.2 subunit. | |
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MedLine Citation:
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PMID: 22677788 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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L-type voltage gated calcium channels (VGCCs) interact with a variety of proteins that modulate both their function and localization. A-Kinase Anchoring Proteins (AKAPs) facilitate L-type calcium channel phosphorylation through β adrenergic stimulation. Our previous work indicated a role of neuronal AKAP79/150 in the membrane targeting of Ca(V)1.2 L-type calcium channels, which involved a proline rich domain (PRD) in the intracellular II-III loop of the channel.(1) Here, we show that mutation of proline 857 to alanine (P857A) into the PRD does not disrupt the AKAP79-induced increase in Ca(v)1.2 membrane expression. Furthermore, deletion of two other PRDs into the carboxy terminal domain of Ca(V)1.2 did not alter the targeting role of AKAP79. In contrast, the distal carboxy terminus region of the channel directly interacts with AKAP79. This protein-protein interaction competes with a direct association of the channel II-III linker on the carboxy terminal tail and modulates membrane targeting of Ca(V)1.2. Thus, our results suggest that the effects of AKAP79 occur through relief of an autoinhibitory mechanism mediated by intramolecular interactions of Ca(v)1.2 intracellular regions. |
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Authors:
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Christophe Altier; Stefan J Dubel; Christian Barrere; Scott E Jarvis; Stephanie C Stotz; John D Scott; Joel Nargeot; Gerald W Zamponi; Emmanuel Bourinet |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-05-01 |
Journal Detail:
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Title: Channels (Austin, Tex.) Volume: 6 ISSN: 1933-6969 ISO Abbreviation: Channels (Austin) Publication Date: 2012 May-Jun |
Date Detail:
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Created Date: 2012-08-22 Completed Date: 2012-12-07 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 101321614 Medline TA: Channels (Austin) Country: United States |
Other Details:
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Languages: eng Pagination: 157-65 Citation Subset: IM |
Affiliation:
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Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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A Kinase Anchor Proteins
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metabolism* Amino Acid Sequence Animals Calcium Channels, L-Type / chemistry*, genetics, metabolism* Cell Line, Transformed Gene Deletion Humans Mice Molecular Sequence Data Mutation, Missense Oocytes Patch-Clamp Techniques Proline / metabolism Proline-Rich Protein Domains Protein Interaction Domains and Motifs Protein Subunits / chemistry*, genetics, metabolism* Protein Transport / genetics Xenopus |
| Grant Support | |
ID/Acronym/Agency:
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GM482312/GM/NIGMS NIH HHS; R37 GM048231/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/A Kinase Anchor Proteins; 0/AKAP5 protein, human; 0/Calcium Channels, L-Type; 0/Cav1.2 protein, mouse; 0/Protein Subunits; 147-85-3/Proline |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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