Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization
NMDA receptor-dependent synaptic modifications, such as long-term potentiation (LTP) and long-term depression (LTD), are essential for brain development and function. LTD occurs mainly by the removal of AMPA receptors from the postsynaptic membrane, but the underlying molecular mechanisms remain unc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/96057 |
| _version_ | 1826208407290380288 |
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| author | Li, Zheng Jo, Jihoon Jia, Jie-Min Lo, Shih-Ching Whitcomb, Daniel J. Jiao, Song Cho, Kwangwook Sheng, Morgan |
| author2 | Picower Institute for Learning and Memory |
| author_facet | Picower Institute for Learning and Memory Li, Zheng Jo, Jihoon Jia, Jie-Min Lo, Shih-Ching Whitcomb, Daniel J. Jiao, Song Cho, Kwangwook Sheng, Morgan |
| author_sort | Li, Zheng |
| collection | MIT |
| description | NMDA receptor-dependent synaptic modifications, such as long-term potentiation (LTP) and long-term depression (LTD), are essential for brain development and function. LTD occurs mainly by the removal of AMPA receptors from the postsynaptic membrane, but the underlying molecular mechanisms remain unclear. Here, we show that activation of caspase-3 via mitochondria is required for LTD and AMPA receptor internalization in hippocampal neurons. LTD and AMPA receptor internalization are blocked by peptide inhibitors of caspase-3 and -9. In hippocampal slices from caspase-3 knockout mice, LTD is abolished whereas LTP remains normal. LTD is also prevented by overexpression of the anti-apoptotic proteins XIAP or Bcl-xL, and by a mutant Akt1 protein that is resistant to caspase-3 proteolysis. NMDA receptor stimulation that induces LTD transiently activates caspase-3 in dendrites, without causing cell death. These data indicate an unexpected causal link between the molecular mechanisms of apoptosis and LTD. |
| first_indexed | 2024-09-23T14:05:16Z |
| format | Article |
| id | mit-1721.1/96057 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:05:16Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/960572022-10-01T19:04:00Z Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization Li, Zheng Jo, Jihoon Jia, Jie-Min Lo, Shih-Ching Whitcomb, Daniel J. Jiao, Song Cho, Kwangwook Sheng, Morgan Picower Institute for Learning and Memory Li, Zheng Sheng, Morgan NMDA receptor-dependent synaptic modifications, such as long-term potentiation (LTP) and long-term depression (LTD), are essential for brain development and function. LTD occurs mainly by the removal of AMPA receptors from the postsynaptic membrane, but the underlying molecular mechanisms remain unclear. Here, we show that activation of caspase-3 via mitochondria is required for LTD and AMPA receptor internalization in hippocampal neurons. LTD and AMPA receptor internalization are blocked by peptide inhibitors of caspase-3 and -9. In hippocampal slices from caspase-3 knockout mice, LTD is abolished whereas LTP remains normal. LTD is also prevented by overexpression of the anti-apoptotic proteins XIAP or Bcl-xL, and by a mutant Akt1 protein that is resistant to caspase-3 proteolysis. NMDA receptor stimulation that induces LTD transiently activates caspase-3 in dendrites, without causing cell death. These data indicate an unexpected causal link between the molecular mechanisms of apoptosis and LTD. National Institutes of Health (U.S.) (Fellowship F32-NS046126) National Institutes of Health (U.S.). Intramural Research Program National Institute of Mental Health (U.S.) 2015-03-17T19:41:23Z 2015-03-17T19:41:23Z 2010-05 2009-12 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/96057 Li, Zheng, Jihoon Jo, Jie-Min Jia, Shih-Ching Lo, Daniel J. Whitcomb, Song Jiao, Kwangwook Cho, and Morgan Sheng. “Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization.” Cell 141, no. 5 (May 2010): 859–871. © 2010 Elsevier Inc. en_US http://dx.doi.org/10.1016/j.cell.2010.03.053 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Li, Zheng Jo, Jihoon Jia, Jie-Min Lo, Shih-Ching Whitcomb, Daniel J. Jiao, Song Cho, Kwangwook Sheng, Morgan Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization |
| title | Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization |
| title_full | Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization |
| title_fullStr | Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization |
| title_full_unstemmed | Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization |
| title_short | Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization |
| title_sort | caspase 3 activation via mitochondria is required for long term depression and ampa receptor internalization |
| url | http://hdl.handle.net/1721.1/96057 |
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