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

PLoS One. 2018 Sep 25;13(9):e0204312. doi: 10.1371/journal.pone.0204312. eCollection 2018.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Ankyrin Repeat*
  • Gene Expression Regulation
  • Humans
  • Muscle Proteins / chemistry*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism
  • Myocardium / metabolism
  • Phylogeny
  • Physical Conditioning, Animal*
  • Sequence Alignment
  • Stress, Physiological
  • Synteny
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish / physiology*

Substances

  • Muscle Proteins

Grants and funding

This study was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Project No. 173008 to DR), bilateral project funded by the German Academic Exchange Service and the Ministry of Education, Science and Technological Development of the Republic of Serbia (Project-ID 451-03-01766/2014-09/3 to SK and 57140778 to DYRS) and the Max Planck Society (DYRS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.