海兔
基因亚型
化学
细胞生物学
生物
生物化学
神经科学
基因
作者
Bindu Raveendra,Ansgar B. Siemer,Sathyanarayanan V. Puthanveettil,Wayne A. Hendrickson,Eric R. Kandel,Ann E. McDermott
摘要
The protein CPEB, required for learning-related synaptic plasticity in the snail Aplysia, has been suggested to convert from a soluble to a prion-like state. Now these conformational forms of Aplysia CPEB are directly observed, with the prion form showing enhanced binding to target mRNAs. The neuronal isoform of cytoplasmic polyadenylation element–binding protein (CPEB) is a regulator of local protein synthesis at synapses and is critical in maintaining learning-related synaptic plasticity in Aplysia. Previous studies indicate that the function of Aplysia CPEB can be modulated by conversion to a stable prion-like state, thus contributing to the stabilization of long-term memory on a molecular level. Here, we used biophysical methods to demonstrate that Aplysia CPEB, like other prions, undergoes a conformational switch from soluble α-helix–rich oligomer to β-sheet–rich fiber in vitro. Solid-state NMR analyses of the fibers indicated a relatively rigid N-terminal prion domain. The fiber form of Aplysia CPEB showed enhanced binding to target mRNAs as compared to the soluble form. Consequently, we propose a model for the Aplysia CPEB fibers that may have relevance for functional prions in general. Although significant knowledge of cellular and molecular mechanisms underlying the acquisition and early storage of implicit and explicit long-term memory has been gained, the mechanisms by which memories are maintained for long periods of time are still not fully understood1,2. Because proteins normally have relatively short half-lives, of hours or days, the question remains: How can the change in molecular composition of a synapse be maintained for long periods of time, as is required for long-term memory? We previously found one answer to this conundrum in a work describing a prion-like regulator of local protein synthesis at the synapse in the marine snail Aplysia californica: the cytoplasmic polyadenylation element–binding protein Aplysia CPEB3,4. This provided physiological evidence that the prion-like properties of Aplysia CPEB might explain the self-sustained, continuous molecular turnover at the synapse5.
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