XIAP Regulates Caspase Activity in Degenerating Axons
Our knowledge of the destructive events that regulate axonal degeneration is rudimentary. Here, we examine the role of caspases and their endogenous inhibitor, the X-linked inhibitor of apoptosis protein (XIAP), in axonal degeneration of dorsal root ganglion (DRG) axons. We show that caspase-3, casp...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713003628 |
| _version_ | 1818808606628249600 |
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| author | Nicolas Unsain Julia M. Higgins Kristen N. Parker Aaron D. Johnstone Philip A. Barker |
| author_facet | Nicolas Unsain Julia M. Higgins Kristen N. Parker Aaron D. Johnstone Philip A. Barker |
| author_sort | Nicolas Unsain |
| collection | DOAJ |
| description | Our knowledge of the destructive events that regulate axonal degeneration is rudimentary. Here, we examine the role of caspases and their endogenous inhibitor, the X-linked inhibitor of apoptosis protein (XIAP), in axonal degeneration of dorsal root ganglion (DRG) axons. We show that caspase-3, caspase-6, and caspase-9 are present in axons and are cleaved upon nerve growth factor (NGF) withdrawal. We observed that caspase-3 activity is high in NGF-withdrawn axons and that CASP3−/− axons are protected from degeneration. XIAP−/− DRG sensory neurons degenerate more rapidly and contain more active caspase-3 than their wild-type counterparts, indicating that axonal caspases are normally regulated by XIAP. Importantly, axonal XIAP levels drop sharply after NGF withdrawal; if XIAP levels are maintained by overexpression, axonal caspase-3 activation and axonal degeneration are suppressed. Finally, we show that XIAP−/− embryos have stunted dermal innervation. We propose that XIAP-mediated caspase inhibition plays an important role in regulating morphogenic events that shape the nervous system during development. |
| first_indexed | 2024-12-18T19:44:14Z |
| format | Article |
| id | doaj.art-d0d1832451b742b99b7346a3a88e78f7 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-18T19:44:14Z |
| publishDate | 2013-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-d0d1832451b742b99b7346a3a88e78f72022-12-21T20:55:21ZengElsevierCell Reports2211-12472013-08-014475176310.1016/j.celrep.2013.07.015XIAP Regulates Caspase Activity in Degenerating AxonsNicolas Unsain0Julia M. Higgins1Kristen N. Parker2Aaron D. Johnstone3Philip A. Barker4Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, CanadaOur knowledge of the destructive events that regulate axonal degeneration is rudimentary. Here, we examine the role of caspases and their endogenous inhibitor, the X-linked inhibitor of apoptosis protein (XIAP), in axonal degeneration of dorsal root ganglion (DRG) axons. We show that caspase-3, caspase-6, and caspase-9 are present in axons and are cleaved upon nerve growth factor (NGF) withdrawal. We observed that caspase-3 activity is high in NGF-withdrawn axons and that CASP3−/− axons are protected from degeneration. XIAP−/− DRG sensory neurons degenerate more rapidly and contain more active caspase-3 than their wild-type counterparts, indicating that axonal caspases are normally regulated by XIAP. Importantly, axonal XIAP levels drop sharply after NGF withdrawal; if XIAP levels are maintained by overexpression, axonal caspase-3 activation and axonal degeneration are suppressed. Finally, we show that XIAP−/− embryos have stunted dermal innervation. We propose that XIAP-mediated caspase inhibition plays an important role in regulating morphogenic events that shape the nervous system during development.http://www.sciencedirect.com/science/article/pii/S2211124713003628 |
| spellingShingle | Nicolas Unsain Julia M. Higgins Kristen N. Parker Aaron D. Johnstone Philip A. Barker XIAP Regulates Caspase Activity in Degenerating Axons Cell Reports |
| title | XIAP Regulates Caspase Activity in Degenerating Axons |
| title_full | XIAP Regulates Caspase Activity in Degenerating Axons |
| title_fullStr | XIAP Regulates Caspase Activity in Degenerating Axons |
| title_full_unstemmed | XIAP Regulates Caspase Activity in Degenerating Axons |
| title_short | XIAP Regulates Caspase Activity in Degenerating Axons |
| title_sort | xiap regulates caspase activity in degenerating axons |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713003628 |
| work_keys_str_mv | AT nicolasunsain xiapregulatescaspaseactivityindegeneratingaxons AT juliamhiggins xiapregulatescaspaseactivityindegeneratingaxons AT kristennparker xiapregulatescaspaseactivityindegeneratingaxons AT aarondjohnstone xiapregulatescaspaseactivityindegeneratingaxons AT philipabarker xiapregulatescaspaseactivityindegeneratingaxons |