Actin maturation requires the ACTMAP/C19orf54 protease

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Protein synthesis typically initiates with methionine, which is usually removed during translation.
• Cytoplasmic actin undergoes a unique post-translational modification involving the removal of acetylated methionine by an unknown enzyme.

Purpose of the Study:

• To identify the enzyme responsible for the noncanonical post-translational modification of actin.
• To investigate the in vivo function of this enzyme in actin maturation and its role in muscle physiology.

Main Methods:

• Enzyme identification through genetic screening and biochemical assays.
• Generation and analysis of knockout mice lacking the identified enzyme.
• Assessment of cytoskeletal structure, actin filament length, muscle function, and histological features in mutant mice.

Main Results:

• C19orf54, designated ACTMAP (actin maturation protease), was identified as the enzyme responsible for removing acetylated methionine from actin.
• Ablation of ACTMAP resulted in mice with immature actin across all tissues.
• Skeletal muscles of ACTMAP-deficient mice exhibited shorter sarcomeric actin filaments, reduced muscle function, and progressive accumulation of centralized nuclei, indicative of myopathy.

Conclusions:

• ACTMAP is the crucial enzyme for producing mature cytoplasmic actin.
• ACTMAP plays a vital role in maintaining normal actin filament length and muscle function.
• Deficiency in ACTMAP leads to actin-related myopathies.