Loss of MEC-17 Leads to Microtubule Instability and Axonal Degeneration
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 id...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-01-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713007341 |
| _version_ | 1831804565741109248 |
|---|---|
| author | Brent Neumann Massimo A. Hilliard |
| author_facet | Brent Neumann Massimo A. Hilliard |
| author_sort | Brent Neumann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T19:08:54Z |
| format | Article |
| id | doaj.art-fdc3ab234bc940fdb38c67e82dc93a58 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T19:08:54Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-fdc3ab234bc940fdb38c67e82dc93a582022-12-21T18:15:44ZengElsevierCell Reports2211-12472014-01-01619310310.1016/j.celrep.2013.12.004Loss of MEC-17 Leads to Microtubule Instability and Axonal DegenerationBrent Neumann0Massimo A. Hilliard1Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, AustraliaQueensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, AustraliaAxonal 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.http://www.sciencedirect.com/science/article/pii/S2211124713007341 |
| spellingShingle | Brent Neumann Massimo A. Hilliard Loss of MEC-17 Leads to Microtubule Instability and Axonal Degeneration Cell Reports |
| title | Loss of MEC-17 Leads to Microtubule Instability and Axonal Degeneration |
| title_full | Loss of MEC-17 Leads to Microtubule Instability and Axonal Degeneration |
| title_fullStr | Loss of MEC-17 Leads to Microtubule Instability and Axonal Degeneration |
| title_full_unstemmed | Loss of MEC-17 Leads to Microtubule Instability and Axonal Degeneration |
| title_short | Loss of MEC-17 Leads to Microtubule Instability and Axonal Degeneration |
| title_sort | loss of mec 17 leads to microtubule instability and axonal degeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713007341 |
| work_keys_str_mv | AT brentneumann lossofmec17leadstomicrotubuleinstabilityandaxonaldegeneration AT massimoahilliard lossofmec17leadstomicrotubuleinstabilityandaxonaldegeneration |