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Ankrd1 inhibits the FAK/Rho-GTPase/F-actin pathway by downregulating ITGA6 transcriptional to regulate myoblast

Cheng Huang1, Qiqi Zhong1, Weisi Lian1

  • 1Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of the Ministry of Education, Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China.

Journal of Cellular Physiology
|July 11, 2024
PubMed

Insights

Ankrd1 knockdown decreases skeletal muscle cell proliferation but enhances differentiation by activating the focal adhesion kinase (FAK)/F-actin pathway. This study reveals Ankrd1 as a key regulator in muscle development and disease.

Area of Science:

  • Muscle Biology
  • Cellular Regulation
  • Molecular Mechanisms

Background:

  • Skeletal muscle is crucial for organismal function, but its growth regulation is poorly understood.
  • Identifying key regulators of muscle development is essential for understanding related diseases.

Purpose of the Study:

  • To investigate the role of Ankylosis disease 1 (Ankrd1) in skeletal muscle cell proliferation and differentiation.
  • To elucidate the molecular pathways influenced by Ankrd1 in C2C12 myoblasts.

Main Methods:

  • Utilized C2C12 myoblast cell line for experiments.
  • Performed Ankrd1 knockdown and analyzed its effects on cell proliferation and differentiation.
  • Conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and RNA-sequencing analyses.
  • Employed dual-luciferase reporter assays to assess promoter activity.

Main Results:

  • Ankrd1 knockdown reduced C2C12 myoblast proliferation while increasing differentiation.
  • Knockdown activated the focal adhesion kinase (FAK)/F-actin signaling pathway, with significant gene upregulation.
  • Integrin subunit Itga6 promoter activity increased upon Ankrd1 knockdown.
  • FAK phosphorylation was enhanced by altered integrin levels, activating the FAK/Rho-GTPase/F-actin pathway.

Conclusions:

  • Ankrd1 knockdown promotes myoblast differentiation by activating the FAK/Rho-GTPase/F-actin pathway via integrin subunit modulation.
  • Ankrd1 is identified as a potential regulator of skeletal muscle development.
  • Findings offer insights into skeletal muscle growth and provide references for muscle-related diseases.
Keywords:
Ankrd1C2C12 myoblastFAKF‐actindifferentiationintegrin

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