Unknown

Dataset Information

0

Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization.

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.

SUBMITTER: Li Z 

PROVIDER: S-EPMC2909748 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization.

Li Zheng Z   Jo Jihoon J   Jia Jie-Min JM   Lo Shih-Ching SC   Whitcomb Daniel J DJ   Jiao Song S   Cho Kwangwook K   Sheng Morgan M  

Cell 20100501 5

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 pep  ...[more]

Similar Datasets

Unknown MAP1B-dependent Rac activation is required for AMPA receptor endocytosis during long-term depression.
| S-EPMC3746201 | biostudies-literature
Unknown PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression.
| S-EPMC3752261 | biostudies-literature
Unknown The novel caspase-3 substrate Gap43 is involved in AMPA receptor endocytosis and long-term depression.
| S-EPMC3861719 | biostudies-literature
Unknown Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation.
| S-EPMC4236409 | biostudies-literature
Unknown Caspase-2 promotes AMPA receptor internalization and cognitive flexibility via mTORC2-AKT-GSK3β signaling.
| S-EPMC6689033 | biostudies-literature
Unknown The δ2 glutamate receptor gates long-term depression by coordinating interactions between two AMPA receptor phosphorylation sites.
| S-EPMC3593918 | biostudies-literature
Unknown Protein phosphatase 2A inhibition induces cerebellar long-term depression and declustering of synaptic AMPA receptor.
| S-EPMC327207 | biostudies-literature
Unknown A Computational Model for the AMPA Receptor Phosphorylation Master Switch Regulating Cerebellar Long-Term Depression.
| S-EPMC4726815 | biostudies-literature
Unknown Metabotropic NMDA receptor function is required for NMDA receptor-dependent long-term depression.
| S-EPMC3593861 | biostudies-other
Unknown Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction.
| S-EPMC4313856 | biostudies-literature