RRC ID 64467
Author Mok JW, Choi KW.
Title Novel function of N-acetyltransferase for microtubule stability and JNK signaling in Drosophila organ development.
Journal Proc Natl Acad Sci U S A
Abstract Regulation of microtubule stability is crucial for the maintenance of cell structure and function. While the acetylation of α-tubulin lysine 40 by acetylase has been implicated in the regulation of microtubule stability, the in vivo functions of N-terminal acetyltransferases (NATs) involved in the acetylation of N-terminal amino acids are not well known. Here, we identify an N-terminal acetyltransferase, Mnat9, that regulates cell signaling and microtubule stability in Drosophila Loss of Mnat9 causes severe developmental defects in multiple tissues. In the wing imaginal disc, Mnat9 RNAi leads to the ectopic activation of c-Jun N-terminal kinase (JNK) signaling and apoptotic cell death. These defects are suppressed by reducing the level of JNK signaling. Overexpression of Mnat9 can also inhibit JNK signaling. Mnat9 colocalizes with mitotic spindles, and its loss results in various spindle defects during mitosis in the syncytial embryo. Furthermore, overexpression of Mnat9 enhances microtubule stability. Mnat9 is physically associated with microtubules and shows a catalytic activity in acetylating N-terminal peptides of α- and β-tubulin in vitro. Cell death and tissue loss in Mnat9-depleted wing discs are restored by reducing the severing protein Spastin, suggesting that Mnat9 protects microtubules from its severing activity. Remarkably, Mnat9 mutated in the acetyl-CoA binding site is as functional as its wild-type form. We also find that human NAT9 can rescue Mnat9 RNAi phenotypes in flies, indicating their functional conservation. Taken together, we propose that Mnat9 is required for microtubule stability and regulation of JNK signaling to promote cell survival in developing Drosophila organs.
Volume 118(4)
Published 2021-1-26
DOI 10.1073/pnas.2010140118
PII 2010140118
PMID 33479178
PMC PMC7848706
MeSH Animals Apoptosis / genetics Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Embryonic Development / genetics Gene Expression Regulation, Developmental / genetics Imaginal Discs / growth & development Imaginal Discs / metabolism JNK Mitogen-Activated Protein Kinases / genetics* Microtubules / genetics Mitosis / genetics N-Terminal Acetyltransferases / genetics* Signal Transduction / genetics Wings, Animal / growth & development Wings, Animal / metabolism
IF 9.412
Drosophila DGRC#104863 DGRC#109126 DGRC#109029