NR APRR
AU Si,K.; Lindquist,S.L.; Kandel,E.R.
TI A neuronal isoform of the aplysia CPEB has prion-like properties
QU Cell 2003 Dec 26; 115(7): 879-91
KI Cell. 2003 Dec 26;115(7):767-8. PMID: 14697195
PT journal article
AB 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.
MH Animals; Aplysia; Glutamine/metabolism; Memory/physiology; Neuronal Plasticity/physiology; Neurons/*metabolism; Prions/genetics/*metabolism; Protein Conformation; Protein Folding; Protein Isoforms/genetics/metabolism; Protein Structure, Tertiary/physiology; RNA, Messenger/metabolism; Saccharomyces cerevisiae; Support, Non-U.S. Gov't; Synaptic Transmission/physiology; Transcription Factors/genetics/*metabolism; Translation, Genetic/*physiology; Xenopus Proteins/genetics/*metabolism
AD 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. ks560@columbia.edu
SP englisch
PO USA