정상 프리온 단백질, 기억력 유지 역할
미국 미주리주 의학연구소 카우식 시 박사와 콜롬비아대 에릭 캔달 박사 팀이 최근 [Cell]지에 발표한 논문입니다.
연구팀은 수십 년간 갯민숭달팽이(일명 바다달팽이)를 대상으로 기억력과 학습능력에 대한 실험을 했습니다. 연구결과, 기억이 저장될 때 신경접합부인 시냅스 속에서 세포질 폴리아데닌화 인자 결합(CPEB) 단백질이 프리온 상태가 된다는 사실을 발견했습니다.
Aplysia CPEB Can Form Prion-like Multimers in Sensory Neurons that Contribute to Long-Term Facilitation
Kausik Si, Yun-Beom Choi, Erica White-Grindley, Amitabha Majumdar, Eric R. Kandel.
출처 : Cell, 5 February 2010, 140(3) pp. 421 – 435.
DOI: 10.1016/j.cell.2010.01.008
http://www.cell.com/abstract/S0092-8674(10)00009-7?script=true
Kausik Si1, 2, 
, 
, Yun-Beom Choi5, 6, Erica White-Grindley1, Amitabha Majumdar1 and Eric R. Kandel3, 4, 5
1 Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA
2 Department of Molecular & Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
3 Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 722 West 168th Street, New York, NY 10032, USA
4 Kavli Institute for Brain Science, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 722 West 168th Street, New York, NY 10032, USA
5 Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 722 West 168th Street, New York, NY 10032, USA
6 Department of Neurology, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 722 West 168th Street, New York, NY 10032, USA
Corresponding author
Graphical Abstract
Highlights
► The Aplysia translational regulator ApCPEB has prion-like properties in neurons ► Exogenously expressed ApCPEB forms self-sustaining amyloidogenic multimers ► Serotonin enhances formation of exogenous ApCPEB multimers ► Inhibition of ApCPEB multimers blocks persistence of long-term facilitation
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Summary
- 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.
