| Autor: |
Haahr P; Division of Biochemistry, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands.; Novo Nordisk Foundation Center for Protein Research (NNF-CPR), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Galli RA; Department of Physiology, Amsterdam UMC (VUmc), 1081HV Amsterdam, Netherlands., van den Hengel LG; Division of Biochemistry, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands.; Oncode Institute, Division of Biochemistry, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands., Bleijerveld OB; Proteomics Facility, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands., Kazokaitė-Adomaitienė J; Protein Facility, Division of Biochemistry, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands., Song JY; Animal Pathology, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands., Kroese LJ; Animal Modeling Facility, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands., Krimpenfort P; Animal Modeling Facility, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands., Baltissen MP; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, 6525GA Nijmegen, Netherlands., Vermeulen M; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, 6525GA Nijmegen, Netherlands., Ottenheijm CAC; Department of Physiology, Amsterdam UMC (VUmc), 1081HV Amsterdam, Netherlands., Brummelkamp TR; Division of Biochemistry, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands.; Oncode Institute, Division of Biochemistry, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands. |
| Abstrakt: |
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. |
