期刊
CELL
卷 141, 期 5, 页码 859-871出版社
CELL PRESS
DOI: 10.1016/j.cell.2010.03.053
关键词
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资金
- NIH [F32-NS046126]
- NIMH
- BBSRC
- Alzheimer's Research Trust UK
- BBSRC [BB/G003963/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/G003963/1] Funding Source: researchfish
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.
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