Profiling of skeletal muscle Ankrd2 protein in human cardiac tissue and neonatal rat cardiomyocytes

Jasnic-Savovic, Jovana; Nestorovic, Aleksandra; Savić, Slobodan; Karasek, Siniša F.; Vitulo, Nicola; Valle, Giorgio; Faulkner, Georgine; Radojković, Dragica; Kojić, Snežana

doi:10.1007/s00418-015-1307-5

Cited by 15 publications

(10 citation statements)

References 57 publications

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“…1e ). ID association for both proteins was recently also described by Jasnic-Savovic and colleagues 35 . Consistent with a previously reported interaction between CARP1 and phospholipase-C (PLC) 36 , we demonstrated in pull-down assays that the coiled coil region of PLCβ1, the main PLC isoform in hearts 37 , binds to both CARP1 and CARP2 ( Fig.…”

Section: Resultssupporting

confidence: 55%

MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy

et al. 2016

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MLP (muscle LIM protein)-deficient mice count among the first mouse models for dilated cardiomyopathy (DCM), yet the exact role of MLP in cardiac signalling processes is still enigmatic. Elevated PKCα signalling activity is known to be an important contributor to heart failure. Here we show that MLP directly inhibits the activity of PKCα. In end-stage DCM, PKCα is concentrated at the intercalated disc of cardiomyocytes, where it is sequestered by the adaptor protein CARP in a multiprotein complex together with PLCβ1. In mice deficient for both MLP and CARP the chronic PKCα signalling chain at the intercalated disc is broken and they remain healthy. Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCα and that chronic uninhibited PKCα activity at the intercalated disc in the absence of functional MLP leads to heart failure.

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Section: Resultssupporting

confidence: 55%

MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy

et al. 2016

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“…Studies on the localization of ANKRD1 have yielded differing results. Jasnic-Savovic et al 27 demonstrated a strong positive immunoreaction for ANKRD1 in the cytoplasm, which coincided with striation of the sarcomere, although ANKRD1 was not detected in the nucleus. The absence of ANKRD1 in the nucleus was confirmed by Ishiguro et al 28 However, Zou et al 11 found ANKRD1 expression in the nuclei of rodent cultured cardiac cells, and several studies have demonstrated that ANKRD1 has a dual subcellular localization, where FIGURE 4 P.S187F mutation modulates the localization of exogenous ANKRD1 in HEK293 cells.…”

Section: Discussionmentioning

confidence: 95%

“…Studies on the localization of ANKRD1 have yielded differing results. Jasnic‐Savovic et al . demonstrated a strong positive immunoreaction for ANKRD1 in the cytoplasm, which coincided with striation of the sarcomere, although ANKRD1 was not detected in the nucleus.…”

Section: Discussionmentioning

confidence: 98%

Ankyrin repeat domain 1: A novel gene for cardiac septal defects

Yang

Xia

et al. 2019

The Journal of Gene Medicine

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Introduction Cardiac septal defects account for more than 50% of congenital heart defects. Ankyrin repeat domain 1 (ANKRD1) is an important transcription factor that is mutated in multiple cardiac diseases; however, a relationship between the ANKRD1 mutation and cardiac septal defects has not been described. Methods We examined genetic mutations in a large family with three cardiac septal defect patients. Whole exome sequencing, bioinformatics and conservation analysis were utilized to predict the pathogenicity of candidate mutations. Dual luciferase reporter assay and nuclear localization experiments were performed to evaluate the influence of target mutation. Results A heterozygous, missense variant of ANKRD1 (MIM* 609599): NM_014391: exon6: c.C560T:p.S187F was identified at a highly conserved region. Sanger sequencing in extended family members demonstrated an incomplete inheritance model. When co‐activated with NKX2.5, ANKRD1 repressed ANF expression as assessed by a dual‐luciferase reporter assay, and p.S187F mutation enhanced the repressive effect (0.318 ± 0.018 versus 0.564 ± 0.048, p < 0.01). A real‐time polymerase chain reaction confirmed that p.S187F mutation of ANKRD1 decreased the expression of endogenous ANF (0.85 ± 0.05 versus 0.61 ± 0.04, p < 0.01). Furthermore, nuclear localization experiments demonstrated that the mutation significantly decreased the nuclear distribution of ANKRD1. Conclusions The present study is the first to identify the p.S187F mutant of ANKRD1, which is associated with cardiac septal defects.

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“…Expression of MARPs in adult mammalian skeletal muscle and the heart is well documented [ 3 – 5 , 59 , 63 ]. In humans, ANKRD1 and ANKRD2 were detected mostly in the heart and skeletal muscles, respectively.…”

Section: Discussionmentioning

confidence: 99%

Characterization of zebrafish (Danio rerio) muscle ankyrin repeat proteins reveals their conserved response to endurance exercise

et al. 2018

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Muscle proteins with ankyrin repeats (MARPs) ANKRD1 and ANKRD2 are titin-associated proteins with a putative role as transcriptional co-regulators in striated muscle, involved in the cellular response to mechanical, oxidative and metabolic stress. Since many aspects of the biology of MARPs, particularly exact mechanisms of their action, in striated muscle are still elusive, research in this field will benefit from novel animal model system. Here we investigated the MARPs found in zebrafish for protein structure, evolutionary conservation, spatiotemporal expression profiles and response to increased muscle activity. Ankrd1 and Ankrd2 show overall moderate conservation at the protein level, more pronounced in the region of ankyrin repeats, motifs indispensable for their function. The two zebrafish genes, ankrd1a and ankrd1b, counterparts of mammalian ANKRD1/Ankrd1, have different expression profiles during first seven days of development. Mild increase of ankrd1a transcript levels was detected at 72 hpf (1.74±0.24 fold increase relative to 24 hpf time point), while ankrd1b expression was markedly upregulated from 24 hpf onward and peaked at 72 hpf (92.18±36.95 fold increase relative to 24 hpf time point). Spatially, they exhibited non-overlapping expression patterns during skeletal muscle development in trunk (ankrd1a) and tail (ankrd1b) somites. Expression of ankrd2 was barely detectable. Zebrafish MARPs, expressed at a relatively low level in adult striated muscle, were found to be responsive to endurance exercise training consisting of two bouts of 3 hours of forced swimming daily, for five consecutive days. Three hours after the last exercise bout, ankrd1a expression increased in cardiac muscle (6.19±5.05 fold change), while ankrd1b and ankrd2 were upregulated in skeletal muscle (1.97±1.05 and 1.84±0.58 fold change, respectively). This study provides the foundation to establish zebrafish as a novel in vivo model for further investigation of MARPs function in striated muscle.

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Profiling of skeletal muscle Ankrd2 protein in human cardiac tissue and neonatal rat cardiomyocytes

Cited by 15 publications

References 57 publications

MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy

MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy

Ankyrin repeat domain 1: A novel gene for cardiac septal defects

Characterization of zebrafish (Danio rerio) muscle ankyrin repeat proteins reveals their conserved response to endurance exercise

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