Aplysia CPEB Can Form Prion-like Multimers in Sensory Neurons that Contribute to Long-Term Facilitation

Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Cell (Impact Factor: 32.24). 02/2010; 140(3):421-35. DOI: 10.1016/j.cell.2010.01.008
Source: PubMed


Prions are proteins that can assume at least two distinct conformational states, one of which is dominant and self-perpetuating. Previously we found that a translation regulator CPEB from Aplysia, ApCPEB, that stabilizes activity-dependent changes in synaptic efficacy can display prion-like properties in yeast. Here we find that, when exogenously expressed in sensory neurons, ApCPEB can form an amyloidogenic self-sustaining multimer, consistent with it being a prion-like protein. In addition, we find that conversion of both the exogenous and the endogenous ApCPEB to the multimeric state is enhanced by the neurotransmitter serotonin and that an antibody that recognizes preferentially the multimeric ApCPEB blocks persistence of synaptic facilitation. These results are consistent with the idea that ApCPEB can act as a self-sustaining prion-like protein in the nervous system and thereby might allow the activity-dependent change in synaptic efficacy to persist for long periods of time.

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    • "According to the neuro-physiological studies by Si et al. (2010) and Majumdar et al. (2012), most of the memory is short-term. The main memory element – a neuron – has a great number of synapses (about 3 10 synapses per neuron) and can possess a plurality of states. "
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    • "Numerous mathematical models have been developed that hypothesize and describe maintenance of long-term memory (LTM) as dependent on bistability of synaptic weights, mediated by positive feedback loops of biochemical reactions, typically thought of as operative in dendritic spines. Proposed feedback mechanisms have relied on self-sustaining autophosphorylation of CaM kinase II (Lisman and Goldring, 1988; Miller et al., 2005), persistent phosphorylation of AMPA receptors by protein kinase A (Hayer and Bhalla, 2005), enhanced translation of protein kinase M ζ (Smolen et al., 2012), or selfsustaining clustering of a translation activator, cytoplasmic polyadenylation element binding protein (Si et al., 2010). With these models, LTP switches a synapse from a state of low basal weight to a high weight state, and also turns on the positive feedback loop. "
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