Naa80 is required for actin N-terminal acetylation and normal hearing in zebrafish

Actin is a critical component of the eukaryotic cytoskeleton. In animals, actins undergo unique N-terminal processing by dedicated enzymes resulting in mature acidic and acetylated forms. The final step, N-terminal acetylation, is catalyzed by NAA80 in humans. N-terminal acetylation of actin is cruc...

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Bibliographic Details
Published in:Life science alliance 2024-12, Vol.7 (12), p.e202402795
Main Authors: Ree, Rasmus, Lin, Sheng-Jia, Sti Dahl, Lars Ole, Huang, Kevin, Petree, Cassidy, Varshney, Gaurav K, Arnesen, Thomas
Format: Article
Language:English
Subjects:
Acetylation
Acetyltransferases - genetics
Acetyltransferases - metabolism
Actins - metabolism
Animals
Hearing - physiology
Humans
Zebrafish - metabolism
Zebrafish Proteins - genetics
Zebrafish Proteins - metabolism
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Summary:Actin is a critical component of the eukaryotic cytoskeleton. In animals, actins undergo unique N-terminal processing by dedicated enzymes resulting in mature acidic and acetylated forms. The final step, N-terminal acetylation, is catalyzed by NAA80 in humans. N-terminal acetylation of actin is crucial for maintaining normal cytoskeletal dynamics and cell motility in human cell lines. However, the physiological impact of actin N-terminal acetylation remains to be fully understood. We developed a zebrafish knockout model and demonstrated that Naa80 acetylates both muscle and non-muscle actins in vivo. Assays with purified Naa80 revealed a preference for acetylating actin N-termini. Zebrafish lacking actin N-terminal acetylation exhibited normal development, morphology, and behavior. In contrast, humans with pathogenic actin variants can present with hypotonia and hearing impairment. Whereas zebrafish lacking showed no obvious muscle defects or abnormalities, we observed abnormal inner ear development, small otoliths, and impaired response to sound. In conclusion, we have established that zebrafish Naa80 N-terminally acetylates actins in vitro and in vivo, and that actin N-terminal acetylation is essential for normal hearing.
ISSN:2575-1077
2575-1077
DOI:10.26508/lsa.202402795