Functional Prions: A Perspective

Status: This talk is in preparation - details may change

Long-term memory storage depends on transcription in the nucleus, an organelle shared by all synapses of a neuron. This raises a question: Are long-term changes cell-wide, or can induced gene products be spatially compartmentalized so that they selectively alter the function of some synapses and not others? In Aplysia, a neuron-specific isoform of cytoplasmic polyadenylation element–binding protein (CPEB) regulates local synaptic protein synthesis. Local protein synthesis serves two functions: (1) it marks the activated synapse and thus confers synapse specificity, and (2) it stabilizes the synaptic growth associated with long-term memory. CPEB may serve as a stabilizer because it has prion-like properties. Prion proteins have the unusual ability to fold into functionally distinct conformations, one of which is self-perpetuating. The dominant, prion-like form of CPEB has the greatest capacity to stimulate translation of CPEB-regulated mRNA. Conversion of CPEB to a prion-like state in stimulated synapses may help to maintain long-term synaptic changes associated with memory storage.