TY - JOUR
T1 - Actin maturation requires the ACTMAP/C19orf54 protease
AU - Haahr, Peter
AU - Galli, Ricardo A.
AU - van den Hengel, Lisa G.
AU - Bleijerveld, Onno B.
AU - Kazokaite-Adomaitiene, Justina
AU - Song, Ji Ying
AU - Kroese, Lona J.
AU - Krimpenfort, Paul
AU - Baltissen, Marijke P.
AU - Vermeulen, Michiel
AU - Ottenheijm, Coen A.C.
AU - Brummelkamp, Thijn R.
N1 - Publisher Copyright:
© 2022 American Association for the Advancement of Science. All rights reserved.
PY - 2022/9/30
Y1 - 2022/9/30
N2 - 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.
AB - 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.
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U2 - 10.1126/science.abq5082
DO - 10.1126/science.abq5082
M3 - Article
C2 - 36173861
AN - SCOPUS:85138973746
SN - 0036-8075
VL - 377
SP - 1533
EP - 1537
JO - Science
JF - Science
IS - 6614
ER -