Loss of MEC-17 leads to microtubule instability and axonal degeneration

Brent Neumann, Massimo A Hilliard

Research output: Contribution to journalArticleResearchpeer-review

42 Citations (Scopus)

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 alpha-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.
Original languageEnglish
Pages (from-to)93-103
Number of pages11
JournalCell Reports
Volume6
Issue number1
DOIs
Publication statusPublished - 16 Jan 2014
Externally publishedYes

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