title: Loss of MEC-17 leads to microtubule instability and axonal degeneration.
abstract: Axonal degeneration arises as a consequence of neuronal injury and is a common hallmark of a number of neurodegenerative diseases. However, the genetic causes and the cellular mechanisms that trigger this process are still largely unknown. Based on forward genetic screening in C. elegans, we have identified the α-tubulin acetyltransferase gene mec-17 as causing spontaneous, adult-onset, and progressive axonal degeneration. Loss of MEC-17 leads to microtubule instability, a reduction in mitochondrial number, and disrupted axonal transport, with altered distribution of both mitochondria and synaptic components. Furthermore, mec-17-mediated axonal degeneration occurs independently from its acetyltransferase domain; is enhanced by mutation of coel-1, a tubulin-associated molecule; and correlates with the animal's body length. This study therefore identifies a critical role for the conserved microtubule-associated protein MEC-17 in preserving axon integrity and preventing axonal degeneration.
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Brent
authors.initials: B
authors.lastname: Neumann
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: m.hilliard@uq.edu.au.
authors.forename: Massimo A
authors.initials: MA
authors.lastname: Hilliard
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation
chemical_list: D029742:Caenorhabditis elegans Proteins; D000123:Acetyltransferases; C552528:MEC-17 protein, C elegans