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

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.

Aflatoxin B1 decreased flesh flavor and inhibited muscle development in grass carp (Ctenopharyngodon idella)

“…Among MRF, muscle cell proliferation is mainly controlled by Myf5 and MyoD, while differentiation is primarily controlled by MRF4 and MyoG in muscle development ( Song et al., 2015 ). There is a high level of expression of MYHC in differentiated myoblasts, which promotes cell fusion and leads to the formation of myotubes ( Zi et al., 2022 ). Our findings demonstrated that AFB1 downregulated MyoG , MyoD , MRF4 , Myf5 , and MYHC mRNA expression in grass carp muscle.…”

Role of Actin-Binding Proteins in Skeletal Myogenesis

“…RhoA and Rac1 have been shown to positively regulate myogenic differentiation through serum response factor (SRF) and β-catenin/TGF, which activate the expression of MyoD, thereby promoting myogenesis [79,80]. Moreover, the interaction of PFN1 with Cdc42, a GTPase protein, has been shown to stimulate PAK/JNK signaling pathways, altering cytoskeletal dynamics and inhibiting myogenic differentiation [81]. In a study by Kooij et al, overexpression of PFN2a in Drosophila resulted in reduced climbing ability of flight muscles, diminished flight capability, and elongated thin filaments [82].…”

Molecular Regulation of Porcine Skeletal Muscle Development: Insights from Research on CDC23 Expression and Function

“…Fu et al [27] have reported that Egl nine homolog 3 (EGLN3, also known as PHD3) regulates skeletal muscle differentiation by modulating the stability of the myogenin protein. Cell division control protein 42 homolog (Cdc42) has been identified as a negative regulator of the differentiation of skeletal muscle cells [28]. Similarly, the homeobox protein Hox-A11 has a significant inhibitory effect on myogenesis during muscle differentiation [29].…”