Si Kausik, Lindquist Susan, Kandel Eric R
Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 722 West 168th Street, New York, NY 10032, USA.
Cell. 2003 Dec 26;115(7):879-91. doi: 10.1016/s0092-8674(03)01020-1.
Prion proteins have the unusual capacity to fold into two functionally distinct conformations, one of which is self-perpetuating. When yeast prion proteins switch state, they produce heritable phenotypes. We report prion-like properties in a neuronal member of the CPEB family (cytoplasmic polyadenylation element binding protein), which regulates mRNA translation. Compared to other CPEB family members, the neuronal protein has an N-terminal extension that shares characteristics of yeast prion-determinants: a high glutamine content and predicted conformational flexibility. When fused to a reporter protein in yeast, this region confers upon it the epigenetic changes in state that characterize yeast prions. Full-length CPEB undergoes similar changes, but surprisingly it is the dominant, self-perpetuating prion-like form that has the greatest capacity to stimulate translation of CPEB-regulated mRNA. We hypothesize that conversion of CPEB to a prion-like state in stimulated synapses helps to maintain long-term synaptic changes associated with memory storage.
朊病毒蛋白具有折叠成两种功能不同构象的非凡能力，其中一种构象能够自我延续。当酵母朊病毒蛋白转变状态时，它们会产生可遗传的表型。我们报道了CPEB家族（细胞质聚腺苷酸化元件结合蛋白）的一个神经元成员具有类朊病毒特性，该蛋白可调节mRNA翻译。与其他CPEB家族成员相比，这种神经元蛋白有一个N端延伸，它具有酵母朊病毒决定簇的特征：谷氨酰胺含量高且预测具有构象灵活性。当在酵母中与报告蛋白融合时，该区域赋予其酵母朊病毒所特有的表观遗传状态变化。全长CPEB也会发生类似变化，但令人惊讶的是，占主导地位的、自我延续的类朊病毒形式具有最大的能力来刺激CPEB调节的mRNA的翻译。我们推测，在受刺激的突触中，CPEB转变为类朊病毒状态有助于维持与记忆存储相关的长期突触变化。
