Loss of zebrafish Smyd1a interferes with myofibrillar integrity without triggering the misfolded myosin response

Paone, Christoph; Rudeck, Steven; Etard, Christelle; Strähle, Uwe; Rottbauer, Wolfgang; Just, Steffen

doi:10.1016/j.bbrc.2018.01.060

Cited by 7 publications

(10 citation statements)

References 18 publications

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“…We showed that, in contrast to smyd1b mutation, loss of smyd1a did not up-regulate hsp90-a1 gene expression. This is consistent with previous findings showing that loss of smyd1a did not trigger misfolded myosin response in zebrafish (26). Smyd1a and Smyd1b are required for slow muscle development Previous studies using MO knockdown and zebrafish mutant showed contradictory findings regarding Smyd1 function in the slow muscle of zebrafish embryos (7)(8)(9)13).…”

Section: Smyd1a Mutation Alone Resulted In No Visible Muscle Defect I...supporting

confidence: 92%

“…However, using the zebrafish smyd1b mutant, flatline ( Fla mvo47a ), it was reported that Smyd1b function was restricted to fast muscles and that the loss of Smyd1b had no effect on slow muscle development (8). Smyd1a function also remains controversial based on 2 morpholino (MO) knockdown studies (11, 26). We have shown that knockdown of smyd1a had no visible effect on muscle development in zebrafish embryos (11).…”

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confidence: 99%

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Defective sarcomere assembly in smyd1a and smyd1b zebrafish mutants

et al. 2019

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Two smyd1 paralogues, smyd1a and smyd1b, have been identified in zebrafish. Although Smyd1b function has been reported in fast muscle, its function in slow muscle and the function of Smyd1a, in general, are uncertain. In this study, we generated 2 smyd1a mutant alleles and analyzed the muscle defects in smyd1a and smyd1b single and double mutants in zebrafish. We demonstrated that knockout of smyd1a alone had no visible effect on muscle development and fish survival. This was in contrast to the smyd1b mutant, which exhibited skeletal and cardiac muscle defects, leading to early embryonic lethality. The smyd1a and smyd1b double mutants, however, showed a stronger muscle defect compared with smyd1a or smyd1b mutation alone, namely, the complete disruption of sarcomere organization in slow and fast muscles. Immunostaining revealed that smyd1a; smyd1b double mutations had no effect on myosin gene expression but resulted in a dramatic reduction of myosin protein levels in muscle cells of zebrafish embryos. This was accompanied by the up‐regulation of hsp40 and hsp90‐α1 gene expression. Together, our studies indicate that both Smyd1a and Smyd1b partake in slow and fast muscle development although Smyd1b plays a dominant role compared with Smyd1a.—Cai, M., Han, L., Liu, L., He, F., Chu, W., Zhang, J., Tian, Z., Du, S. Defective sarcomere assembly in smyd1a and smyd1b zebrafish mutants. FASEB J. 33, 6209–6225 (2019). http://www.fasebj.org

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Section: Smyd1a Mutation Alone Resulted In No Visible Muscle Defect I...supporting

confidence: 92%

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confidence: 99%

Defective sarcomere assembly in smyd1a and smyd1b zebrafish mutants

et al. 2019

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“…crispants) are often genetically mosaics. However, in cases of highly efficient gRNAs, they have been shown to recapitulate mutant phenotypes successfully (Küry et al , ; Teboul et al , ; Paone et al , ). Both psmc3 crispants used in this study displayed a cataract phenotype (100% of gRNA1 + Cas9 ( n = 20) and 95% of gRNA2 + Cas9 ( n = 20), whereas none of the control embryos (injected with gRNA1 ( n = 20) or gRNA2 ( n = 10) without the Cas9 protein) showed abnormal lens reflections (Fig B and B′, and ).…”

Section: Resultsmentioning

confidence: 99%

Proteasome subunit PSMC3 variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress

et al. 2020

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The ubiquitin–proteasome system degrades ubiquitin‐modified proteins to maintain protein homeostasis and to control signalling. Whole‐genome sequencing of patients with severe deafness and early‐onset cataracts as part of a neurological, sensorial and cutaneous novel syndrome identified a unique deep intronic homozygous variant in the PSMC3 gene, encoding the proteasome ATPase subunit Rpt5, which lead to the transcription of a cryptic exon. The proteasome content and activity in patient's fibroblasts was however unaffected. Nevertheless, patient's cells exhibited impaired protein homeostasis characterized by accumulation of ubiquitinated proteins suggesting severe proteotoxic stress. Indeed, the TCF11/Nrf1 transcriptional pathway allowing proteasome recovery after proteasome inhibition is permanently activated in the patient's fibroblasts. Upon chemical proteasome inhibition, this pathway was however impaired in patient's cells, which were unable to compensate for proteotoxic stress although a higher proteasome content and activity. Zebrafish modelling for knockout in PSMC3 remarkably reproduced the human phenotype with inner ear development anomalies as well as cataracts, suggesting that Rpt5 plays a major role in inner ear, lens and central nervous system development.

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“…Due to this specific feature, gene functional redundancy needs to be taken under consideration during zebrafish modeling design. A recent reported example is the redundant roles of zebrafish smyd1a and smyd1b paralogues [23]. At this study, it was shown that both Smyd1a and Smyd1b were localized in skeletal and cardiac muscles and overexpression of smyd1a efficiently compensated the loss of Smyd1b in mutant zebrafish and rescued the provoked myopathic phenotype.…”

Section: The Pool Of Engineering Toolsmentioning

confidence: 65%

On Zebrafish Disease Models and Matters of the Heart

Giardoglou

Beis

2019

Biomedicines

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Coronary artery disease (CAD) is the leading form of cardiovascular disease (CVD), which is the primary cause of mortality worldwide. It is a complex disease with genetic and environmental risk factor contributions. Reports in human and mammalian models elucidate age-associated changes in cardiac function. The diverse mechanisms involved in cardiac diseases remain at the center of the research interest to identify novel strategies for prevention and therapy. Zebrafish (Danio rerio) have emerged as a valuable vertebrate model to study cardiovascular development over the last few decades. The facile genetic manipulation via forward and reverse genetic approaches combined with noninvasive, high-resolution imaging and phenotype-based screening has provided new insights to molecular pathways that orchestrate cardiac development. Zebrafish can recapitulate human cardiac pathophysiology due to gene and regulatory pathways conservation, similar heart rate and cardiac morphology and function. Thus, generations of zebrafish models utilize the functional analysis of genes involved in CAD, which are derived from large-scale human population analysis. Here, we highlight recent studies conducted on cardiovascular research focusing on the benefits of the combination of genome-wide association studies (GWAS) with functional genomic analysis in zebrafish. We further summarize the knowledge obtained from zebrafish studies that have demonstrated the architecture of the fundamental mechanisms underlying heart development, homeostasis and regeneration at the cellular and molecular levels.

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Loss of zebrafish Smyd1a interferes with myofibrillar integrity without triggering the misfolded myosin response

Cited by 7 publications

References 18 publications

Defective sarcomere assembly in smyd1a and smyd1b zebrafish mutants

Defective sarcomere assembly in smyd1a and smyd1b zebrafish mutants

Proteasome subunit PSMC3 variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress

On Zebrafish Disease Models and Matters of the Heart

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