Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
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.
Pubmed ID: 33479178
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Drosophila melanogaster with name P{w[+mC]=UAS-Dcr-2.D}1, w[1118] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMJ30230}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-Dcr-2.D}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name P{ry[+t7.2]=neoFRT}82B kay[2] ca[1]/TM6B, Tb[1] ca[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mW.hs]=en2.4-GAL4}e16E from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-Dcr-2.D}10 from BDSC.
View all literature mentionsDrosophila melanogaster with name P{w[+mC]=UAS-Dcr-2.D}1, w[1118]; P{w[+mW.hs]=GawB}bbg[C96] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[1118]; P{w[+mW.hs]=GawB}pnr[MD237]/TM3, P{w[+mC]=UAS-y.C}MC2, Ser[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Mmp1.f1}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01568}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{y[+t7.7] w[+mC]=UAS-Cas9.P2}attP40/CyO; P{w[+mW.hs]=GawB}bbg[C96] from BDSC.
View all literature mentionsDrosophila melanogaster with name hep[1]/FM6 from BDSC.
View all literature mentionsDrosophila melanogaster with name P{w[+mC]=UAS-Dcr-2.D}1, w[1118]; P{w[+mW.hs]=en2.4-GAL4}e16E, P{w[+mC]=UAS-myr-mRFP}1, P{w[+m*]=NRE-EGFP.S}5A from BDSC.
View all literature mentionsDrosophila melanogaster with name P{w[+mC]=UAS-Dcr-2.D}1, w[1118]; P{w[+mW.hs]=en2.4-GAL4}e16E, P{w[+mC]=UAS-2xEGFP}AH2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; Mmp1[2]/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC03560}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[1118]; P{w[+mC]=UAS-Fra.Fbz}7 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mW.hs]=GawB}nubbin-AC-62; P{y[+t7.7] w[+mC]=UAS-Cas9.P2}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118] P{w[+mC]=UAS-bsk.DN}2 from BDSC.
View all literature mentions