The Caenorhabditis elegans Elongator complex regulates neuronal alpha-tubulin acetylation.
Although acetylated alpha-tubulin is known to be a marker of stable microtubules in neurons, precise factors that regulate alpha-tubulin acetylation are, to date, largely unknown. Therefore, a genetic screen was employed in the nematode Caenorhabditis elegans that identified the Elongator complex as a possible regulator of alpha-tubulin acetylation. Detailed characterization of mutant animals revealed that the acetyltransferase activity of the Elongator is indeed required for correct acetylation of microtubules and for neuronal development. Moreover, the velocity of vesicles on microtubules was affected by mutations in Elongator. Elongator mutants also displayed defects in neurotransmitter levels. Furthermore, acetylation of alpha-tubulin was shown to act as a novel signal for the fine-tuning of microtubules dynamics by modulating alpha-tubulin turnover, which in turn affected neuronal shape. Given that mutations in the acetyltransferase subunit of the Elongator (Elp3) and in a scaffold subunit (Elp1) have previously been linked to human neurodegenerative diseases, namely Amyotrophic Lateral Sclerosis and Familial Dysautonomia respectively highlights the importance of this work and offers new insights to understand their etiology.
Solinger
Jachen A
JA
C. elegans Genetics, IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
Paolinelli
Roberta
R
Klöss
Holger
H
Scorza
Francesco Berlanda
FB
Marchesi
Stefano
S
Sauder
Ursula
U
Mitsushima
Dai
D
Capuani
Fabrizio
F
Stürzenbaum
Stephen R
SR
Cassata
Giuseppe
G
D000107:Acetylation; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D016601:RNA-Binding Proteins; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C118234:MEC-12 protein, C elegans; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D014404:Tubulin; C547653:elpc-1 proteins, C elegans; C538730:ELP3 protein, Drosophila; D051548:Histone Acetyltransferases