Ubiquitin C-Terminal Hydrolase Is an Immediate-Early Gene Essential for Long-Term Facilitation in Aplysia

The switch from short-term to long-term facilitation of the synapses between sensory and motor neurons mediating gill and tail withdrawal reflexes in Aplysia requires CREB-mediated transcription and new protein synthesis. We isolated several downstream genes, one of which encodes a neuron-specific u...

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Veröffentlicht in:Cell 1997-04, Vol.89 (1), p.115-126
Hauptverfasser: Hegde, Ashok N., Inokuchi, Kaoru, Pei, Wanzheng, Casadio, Andrea, Ghirardi, Mirella, Chain, Daniel G., Martin, Kelsey C., Kandel, Eric R., Schwartz, James H.
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Sprache:eng
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Zusammenfassung:The switch from short-term to long-term facilitation of the synapses between sensory and motor neurons mediating gill and tail withdrawal reflexes in Aplysia requires CREB-mediated transcription and new protein synthesis. We isolated several downstream genes, one of which encodes a neuron-specific ubiquitin C-terminal hydrolase. This rapidly induced gene encodes an enzyme that associates with the proteasome and increases its proteolytic activity. This regulated proteolysis is essential for long-term facilitation. Inhibiting the expression or function of the hydrolase blocks induction of long-term but not short-term facilitation. We suggest that the enhanced proteasome activity increases degradation of substrates that normally inhibit long-term facilitation. Thus, through induction of the hydrolase and the resulting up-regulation of the ubiquitin pathway, learning recruits a regulated form of proteolysis that removes inhibitory constraints on long-term memory storage.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)80188-9