Left–right asymmetric ventricular expression of CARP in the piglet heart: regional response to experimental heart failure

Torrado, Mario; López, Ellen D. S.; Centeno, Alberto; Castro‐Beiras, Alfonso; Михайлов, А. И.

doi:10.1016/j.ejheart.2003.11.004

Cited by 35 publications

(79 citation statements)

References 49 publications

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“…Piglet cardiac cDNAs were used for PCR reactions in a Biometra II PCR system to detect different RNAs using the primers indicated in Supplementary table 1. Semiquantitative RT-PCR was performed as described previously (Torrado et al, 2003(Torrado et al, , 2004. Detection of various ankrd1 variants was performed using primers located on exon-exon or exon-intron junctions.…”

Section: Semiquantitative Reverse Transcription-polymerase Chain Reacmentioning

confidence: 99%

“…Total protein lysates were subjected to SDS-PAGE (Mini-Protean-III, Bio-Rad), stained with Coomassie or blotted onto PVDF-membranes (Hybond-P, Amersham Biosciences), and probed with rabbit polyclonal antibodies against porcine ANKRD1 (Torrado et al, 2004) or mouse monoclonal anti-myc or anti-FLAG antibodies (Sigma). Molecular weight (MW) standards (MARK-12 and SeeBlue Plus2 from Invitrogen) were included on each gel.…”

Section: Sds-page and Western Blottingmentioning

confidence: 99%

“…The primary transcript is processed to encode a protein product with an apparent molecular size of 39-40 kDa (Zou et al, 1997;Torrado et al, 2004Torrado et al, , 2006. The degradation motif in the 3′ untranslated region of the ankrd1 mRNA, as well as the potential PEST-like degradation sequence and putative phosphorylation and glycosylation sites suggest that the endogenous expression of ankrd1 can be regulated at both post-transcriptional and post-translational levels (Samaras et al, 2007;Witt et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Distinct 5′ cis regulatory elements of the ankrd1 gene can direct chamber-dependent gene expression, such as atrial versus ventricular and left versus right (Kuo et al, 1999). In this regard, left-right asymmetric patterns of ankrd1 cardiac expression are most obvious in newborn and early-postnatal pigs (Torrado et al, 2004(Torrado et al, , 2006. ANKRD1 was thought to be involved in the regulation of cardiac gene expression during fetal heart development via its interaction with transcription factor YB-1 (Zou et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, ankrd1 has also been identified as a candidate gene that can play an important role in congenital cardiac (Cinquetti et al, 2008) and skeletal muscle (Bakay et al, 2002;Nakada et al, 2003) disease, as well as in angiogenesis (Boengler et al, 2003), neovascularization (Shi et al, 2005;Samaras et al, 2007) and neurite outgrowth (Stam et al, 2007). In in vivo experimental settings, ANKRD1 is used as a surrogate biomarker of cardiac hypertrophy (Aihara et al, 2000), cardio-toxic damage (Torrado et al, 2004) or skeletal myopathy (Casey et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Intron retention generates ANKRD1 splice variants that are co-regulated with the main transcript in normal and failing myocardium

Torrado

Iglesias

Nespereira

et al. 2009

Gene

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The cardiac ankyrin repeat domain 1 protein (ANKRD1, also known as CARP) has been extensively characterized with regard to its proposed functions as a cardio-enriched transcriptional co-factor and stressinducible myofibrillar protein. The present results show the occurrence of alternative splicing by intron retention events in the pig and human ankrd1 gene. In pig heart, ankrd1 is expressed as four alternatively spliced transcripts, three of which have non-excised introns: ankrd1-contained introns 6, 7 and 8 (i.e., ankrd1-i6,7,8), ankrd1-contained introns 7 and 8 (i.e., ankrd1-i7,8), and ankrd1 retained only intron 8 (i.e., ankrd1-i8). In the human heart, two orthologues of porcine intron-retaining ankrd1 variants (i.e., ankrd1-i8 and ankrd1-i7,8) are detected. We demonstrate that these newly-identified intron-retaining ankrd1 transcripts are functionally intact, efficiently translated into protein in vitro and exported to the cytoplasm in cardiomyocytes in vivo. In the piglet heart, both the intronless and intron-retaining ankrd1 mRNAs are co-expressed in a chamber-dependent manner being more abundant in the left as compared to the right myocardium. Our data further indicate co-upregulation of the ankrd1 spliced variants in myocardium in the porcine model of diastolic heart failure. Most significantly, we demonstrate that in vivo forced expression of recombinant intronless ankrd1 markedly increases the levels of intron-retaining ankrd1 variants (but not of the endogenous main transcript) in piglet myocardium, suggesting that ANKRD1 may positively regulate the expression of its own intron-containing RNAs in response to cardiac stress. Overall, our findings demonstrate that in cardiomyocytes ANKRD1 can exist in multiple isoforms which may contribute to the functional diversity of this factor in heart development and disease. Abbreviations ANKRD1, ankyrin repeat domain 1 protein; MARPs, muscle ankyrin repeat proteins; SRF, serum response factor; HF, heart failure; DHF, diastolic HF; LV/RV, left/right ventricular myocardium; LA/RA, left/right atrial

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Section: Semiquantitative Reverse Transcription-polymerase Chain Reacmentioning

confidence: 99%

Section: Sds-page and Western Blottingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intron retention generates ANKRD1 splice variants that are co-regulated with the main transcript in normal and failing myocardium

Torrado

Iglesias

Nespereira

et al. 2009

Gene

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Probing Muscle Ankyrin‐Repeat Protein (MARP) Structure and Function

Lun

Chen

Lange

2014

The Anatomical Record

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Muscle ankyrin-repeat proteins (MARPs) have been shown to serve diverse functions within cardiac and skeletal muscle cells. Apart from their interactions with sarcomeric proteins like titin or myopalladin that locate them along myofilaments, MARPs are able to shuttle to the nucleus where they act as modulators for a variety of transcription factors. The deregulation of MARPs in many cardiac and skeletal myopathies contributes to their use as biomarkers for these diseases. Many of their functions are attributed to their domain composition. MARPs consist of an N-terminal coiled-coil domain responsible for their dimerization. The C-terminus contains a series of ankyrin-repeats, whose best-characterized function is to bind to the N2A-region of the giant sarcomeric protein titin. Here we investigate the nature of their dimerization and their interaction with titin more closely. We demonstrate that the coiled-coil domain in all MARPs enables their homo- and hetero-dimerization in antiparallel fashion. Protein complementation experiments indicate further antiparallel binding of the ankyrin-repeats to titin’s N2A-region. Binding of MARP to titin also affects its PKA mediated phosphorylation. We demonstrate further that MARPs themselves are phosphorylated by PKA and PKC, potentially altering their structure or function. These studies elucidate structural relationships within the stretch-responsive MARP/titin complex in cross-striated muscle cells, and may relate to disease relevant posttranslational modifications of MARPs and titin that alter muscle compliance.

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The cardiac ankyrin repeat domain 1 protein: do you know enough about its dimerization properties?

Михайлов¹,

Torrado²

2006

J Muscle Res Cell Motil

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Left–right asymmetric ventricular expression of CARP in the piglet heart: regional response to experimental heart failure

Cited by 35 publications

References 49 publications

Intron retention generates ANKRD1 splice variants that are co-regulated with the main transcript in normal and failing myocardium

Intron retention generates ANKRD1 splice variants that are co-regulated with the main transcript in normal and failing myocardium

Probing Muscle Ankyrin‐Repeat Protein (MARP) Structure and Function

The cardiac ankyrin repeat domain 1 protein: do you know enough about its dimerization properties?

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