Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization
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Li-2010-Caspase-3 Activation.pdf
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Author(s)
Li, Zheng
Jo, Jihoon
Jia, Jie-Min
Lo, Shih-Ching
Whitcomb, Daniel J.
Jiao, Song
Cho, Kwangwook
Sheng, Morgan
Date Issued
May 2010
Journal
Cell
Publisher
Elsevier
Citation
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.
Version
Final published version
Abstract
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.
MIT Department
Picower Institute for Learning and Memory
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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.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2010.03.053
