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Proteomic profiling of kars knockout zebrafish larvae.

Jingjing Wang1, Xiao Yu1, Ying Wang1

  • 1Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai 200233, China.

Gene
|March 3, 2025
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Summary

KARS deficiency causes complex neurological disorders. Zebrafish proteomic analysis revealed altered protein levels, particularly in ribosome and aminoacyl-tRNA biosynthesis pathways, offering insights into disease mechanisms.

Keywords:
KARSKnockoutMultisystem disordersPRM；ProteomicsZebrafishiTRAQ

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Area of Science:

  • Genetics and Molecular Biology
  • Proteomics
  • Zebrafish Models

Background:

  • KARS encodes lysyl-tRNA synthetase, essential for protein translation.
  • KARS variants are linked to hearing loss, visual disorders, and neurological conditions.
  • Mechanisms of KARS deficiency-related neurological diseases are poorly understood.

Purpose of the Study:

  • To investigate the in vivo molecular mechanisms of KARS deficiency.
  • To identify differentially abundant proteins in KARS-deficient zebrafish.
  • To gain insights into ARS-related disorders.

Main Methods:

  • Developed kars knockout zebrafish model.
  • Performed proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) on zebrafish larvae.
  • Validated differentially abundant proteins (DAPs) using parallel reaction monitoring (PRM).

Main Results:

  • Identified 420 DAPs between knockout and wildtype zebrafish.
  • Enrichment analysis revealed significant alterations in ribosome, aminoacyl-tRNA biosynthesis, and hypertrophic cardiomyopathy pathways.
  • Specific protein changes linked to kars deficiency included nars, mybphb, atp2a1l, col6a1, and rps3a.

Conclusions:

  • This study provides novel in vivo data on KARS deficiency.
  • The findings enhance understanding of molecular mechanisms in KARS-associated diseases.
  • Offers comprehensive insights into aminoacyl-tRNA synthetase-related disorders.