Document Detail


AKAP79 modulation of L-type channels involves disruption of intramolecular interactions in the CaV1.2 subunit.
MedLine Citation:
PMID:  22677788     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-01
Journal Detail:
Title:  Channels (Austin, Tex.)     Volume:  6     ISSN:  1933-6969     ISO Abbreviation:  Channels (Austin)     Publication Date:    2012 May-Jun
Date Detail:
Created Date:  2012-08-22     Completed Date:  2012-12-07     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101321614     Medline TA:  Channels (Austin)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  157-65     Citation Subset:  IM    
Affiliation:
Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada.
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MeSH Terms
Descriptor/Qualifier:
A Kinase Anchor Proteins / 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:
GM482312/GM/NIGMS NIH HHS; R01 GM048231/GM/NIGMS NIH HHS; R37 GM048231/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
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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