Mechanisms for generating the autonomous cAMP-dependent protein kinase required for long-term facilitation in Aplysia

The formation of a persistently active cAMP-dependent protein kinase (PKA) is critical far establishing long-term synaptic facilitation (LTF) in Aplys ia. The injection of bovine catalytic (C) subunits into sensory neurons is sufficient to produce protein synthesis-dependent LTF. Early in the LTF ind uced by serotonin (5-HT), an autonomous PKA is generated through the ubiqui tin-proteasome-mediated proteolysis of regulatory (R) subunits. The degrada tion of R occurs during an early time window and appears to be a key functi on of proteasomes in LTF. Lactacystin, a specific proteasome inhibitor, blo cks the facilitation induced by 5-HT, and this block is rescued by injectin g C subunits. R is degraded through an allosteric mechanism requiring an el evation of cAMP coincident with the induction of a ubiquitin carboxy-termin al hydrolase.