PFN1 Inhibits Myogenesis of Bovine Myoblast Cells via Cdc42-PAK/JNK

Cells. 2022 Oct 11;11(20):3188. doi: 10.3390/cells11203188.

Abstract

Myoblast differentiation is essential for the formation of skeletal muscle myofibers. Profilin1 (Pfn1) has been identified as an actin-associated protein, and has been shown to be critically important to cellular function. Our previous study found that PFN1 may inhibit the differentiation of bovine skeletal muscle satellite cells, but the underlying mechanism is not known. Here, we confirmed that PFN1 negatively regulated the myogenic differentiation of bovine skeletal muscle satellite cells. Immunoprecipitation assay combined with mass spectrometry showed that Cdc42 was a binding protein of PFN1. Cdc42 could be activated by PFN1 and could inhibit the myogenic differentiation like PFN1. Mechanistically, activated Cdc42 increased the phosphorylation level of p2l-activated kinase (PAK), which further activated the phosphorylation activity of c-Jun N-terminal kinase (JNK), whereas PAK and JNK are inhibitors of myogenic differentiation. Taken together, our results reveal that PFN1 is a repressor of bovine myogenic differentiation, and provide the regulatory mechanism.

Keywords: Cdc42; JNK; PAK; PFN1; bovine; myogenic differentiation; skeletal muscle satellite cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins*
  • Animals
  • Cattle
  • Cell Differentiation
  • JNK Mitogen-Activated Protein Kinases
  • Muscle Development
  • Satellite Cells, Skeletal Muscle*

Substances

  • Actins
  • JNK Mitogen-Activated Protein Kinases

Grants and funding

This research was funded by National Natural Science Foundation of China, grant number 31902151; and Scientific Research Program of Tianjin Education Commission, grant number 2018KJ183.