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Publication : Local pruning of dendrites and spines by caspase-3-dependent and proteasome-limited mechanisms.

First Author  Ertürk A Year  2014
Journal  J Neurosci Volume  34
Issue  5 Pages  1672-88
PubMed ID  24478350 Mgi Jnum  J:310735
Mgi Id  MGI:6763748 Doi  10.1523/JNEUROSCI.3121-13.2014
Citation  Erturk A, et al. (2014) Local pruning of dendrites and spines by caspase-3-dependent and proteasome-limited mechanisms. J Neurosci 34(5):1672-88
abstractText  Synapse loss occurs normally during development and pathologically during neurodegenerative disease. Long-term depression, a proposed physiological correlate of synapse elimination, requires caspase-3 and the mitochondrial pathway of apoptosis. Here, we show that caspase-3 activity is essential--and can act locally within neurons--for regulation of spine density and dendrite morphology. By photostimulation of Mito-KillerRed, we induced caspase-3 activity in defined dendritic regions of cultured neurons. Within the photostimulated region, local elimination of dendritic spines and dendrite retraction occurred in a caspase-3-dependent manner without inducing cell death. However, pharmacological inhibition of inhibitor of apoptosis proteins or proteasome function led to neuronal death, suggesting that caspase activation is spatially restricted by these "molecular brakes" on apoptosis. Caspase-3 knock-out mice have increased spine density and altered miniature EPSCs, confirming a physiological involvement of caspase-3 in the regulation of spines in vivo.
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