Control of muscle formation by the fusogenic micropeptide myomixer

Area of Science:

• Molecular Biology
• Developmental Biology
• Cell Biology

Background:

• Skeletal muscle formation involves myoblast fusion into multinucleated myofibers.
• Understanding the genetic regulation of myoblast fusion is crucial for muscle development research.

Purpose of the Study:

• To identify novel genes required for myoblast fusion and myogenesis.
• To characterize the function of a newly discovered muscle-specific peptide in skeletal muscle formation.

Main Methods:

• Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen.
• Analysis of gene expression during myoblast differentiation.
• Immunofluorescence microscopy to determine protein localization.
• Functional assays for cell-cell fusion (fibroblast-fibroblast and fibroblast-myoblast).

Main Results:

• Discovery of Myomixer, an 84-amino acid muscle-specific peptide essential for myoblast fusion.
• Myomixer expression is upregulated during myoblast differentiation and is critical for skeletal muscle formation in embryogenesis.
• Myomixer localizes to the plasma membrane and functions with Myomaker to promote myoblast fusion.
• The Myomixer-Myomaker complex can induce fusion in non-muscle cells.

Conclusions:

• The Myomixer-Myomaker protein pair is a key regulator of myoblast fusion during skeletal muscle development.
• This discovery provides new insights into the molecular mechanisms controlling myofiber formation.
• Myomixer represents a potential target for understanding and treating muscle-related disorders.