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

作者：Ashok N. Hegde, Kaoru Inokuchi, Wanzheng Pei, Andrea Casadio, Mirella Ghirardi, Daniel G. Chain, Kelsey C. Martin, Eric R. Kandel, James H. Schwartz · 发表于：Cell · 年份：1997 · DOI：10.1016/s0092-8674(00)80188-9 · 被引用次数：360 · 研究领域：Ubiquitin and proteasome pathways、Endoplasmic Reticulum Stress and Disease、Genetics and Neurodevelopmental Disorders

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.