RGD Reference Report - The C-terminus of the long AKAP13 isoform (AKAP-Lbc) is critical for development of compensatory cardiac hypertrophy. - Rat Genome Database

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The C-terminus of the long AKAP13 isoform (AKAP-Lbc) is critical for development of compensatory cardiac hypertrophy.

Authors: Taglieri, Domenico M  Johnson, Keven R  Burmeister, Brian T  Monasky, Michelle M  Spindler, Matthew J  DeSantiago, Jaime  Banach, Kathrin  Conklin, Bruce R  Carnegie, Graeme K 
Citation: Taglieri DM, etal., J Mol Cell Cardiol. 2014 Jan;66:27-40. doi: 10.1016/j.yjmcc.2013.10.010. Epub 2013 Oct 23.
RGD ID: 243048462
Pubmed: PMID:24161911   (View Abstract at PubMed)
PMCID: PMC4074493   (View Article at PubMed Central)
DOI: DOI:10.1016/j.yjmcc.2013.10.010   (Journal Full-text)

The objective of this study was to determine the role of A-Kinase Anchoring Protein (AKAP)-Lbc in the development of heart failure, by investigating AKAP-Lbc-protein kinase D1 (PKD1) signaling in vivo in cardiac hypertrophy. Using a gene-trap mouse expressing a truncated version of AKAP-Lbc (due to disruption of the endogenous AKAP-Lbc gene), that abolishes PKD1 interaction with AKAP-Lbc (AKAP-Lbc-ΔPKD), we studied two mouse models of pathological hypertrophy: i) angiotensin (AT-II) and phenylephrine (PE) infusion and ii) transverse aortic constriction (TAC)-induced pressure overload. Our results indicate that AKAP-Lbc-ΔPKD mice exhibit an accelerated progression to cardiac dysfunction in response to AT-II/PE treatment and TAC. AKAP-Lbc-ΔPKD mice display attenuated compensatory cardiac hypertrophy, increased collagen deposition and apoptosis, compared to wild-type (WT) control littermates. Mechanistically, reduced levels of PKD1 activation are observed in AKAP-Lbc-ΔPKD mice compared to WT mice, resulting in diminished phosphorylation of histone deacetylase 5 (HDAC5) and decreased hypertrophic gene expression. This is consistent with a reduced compensatory hypertrophy phenotype leading to progression of heart failure in AKAP-Lbc-ΔPKD mice. Overall, our data demonstrates a critical in vivo role for AKAP-Lbc-PKD1 signaling in the development of compensatory hypertrophy to enhance cardiac performance in response to TAC-induced pressure overload and neurohumoral stimulation by AT-II/PE treatment.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiomegaly  ISOPrkd1 (Mus musculus)243048462; 243048462protein:increased activity:heart (mouse)RGD 
Cardiomegaly  IEP 243048462protein:increased activity:heart (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkd1  (protein kinase D1)

Genes (Mus musculus)
Prkd1  (protein kinase D1)

Genes (Homo sapiens)
PRKD1  (protein kinase D1)


Additional Information