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Updated: Aug 27, 2025
Aip1p Dynamics Are Altered by the R256H Mutation in Actin
Published on: July 30, 2014
Actin maturation requires the ACTMAP/C19orf54 protease
Peter Haahr1,2, Ricardo A Galli3, Lisa G van den Hengel1,4
1Division of Biochemistry, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands.
Abstract:
Protein synthesis generally starts with a methionine that is removed during translation. However, cytoplasmic actin defies this rule because its synthesis involves noncanonical excision of the acetylated methionine by an unidentified enzyme after translation. Here, we identified C19orf54, named ACTMAP (actin maturation protease), as this enzyme. Its ablation resulted in viable mice in which the cytoskeleton was composed of immature actin molecules across all tissues. However, in skeletal muscle, the lengths of sarcomeric actin filaments were shorter, muscle function was decreased, and centralized nuclei, a common hallmark of myopathies, progressively accumulated. Thus, ACTMAP encodes the missing factor required for the synthesis of mature actin and regulates specific actin-dependent traits in vivo.
Insights
Researchers identified ACTMAP as the enzyme that matures actin by removing methionine post-translation. Its absence leads to immature actin, shorter muscle filaments, and myopathy hallmarks in mice.
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.
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