Mutability of prions.
Mutability of prions.
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DOI：
10.1038/embor.2011.191
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发表时间：
2011-12-01
期刊：
影响因子：
7.7
通讯作者：
Weissmann, Charles
中科院分区：
文献类型：
--
作者：
Li, Jiali;Mahal, Sukhvir P.;Mahal, P.;Demczyk, Cheryl A.;Weissmann, Charles
从脑转移到培养细胞的小鼠朊病毒逐渐适应新的环境。脑源性22 L朊病毒可以在苦马豆素（swa）存在下感染神经母细胞瘤源性PK 1细胞;也就是说，它们是“swa抗性”。PK 1细胞适应的22 L朊病毒是swa敏感的，然而，在swa中繁殖导致swa抗性亚株的选择。克隆的，PK 1细胞适应的22 L朊病毒最初无法开发swa抗性（“swa不胜任”），然而，连续繁殖30-90 doubests后，9个克隆中的4个成为swa胜任，表明swa抗性“突变体”在复制过程中出现。在朊病毒的情况下，突变归因于PrPSc构象的可遗传变化。一个克隆即使在1035倍扩增后仍保持swa无能;令人惊讶的是，在脑中繁殖后，它产生了swa抗性朊病毒，与原始的22 L群体无法区分。因此，细胞适应的22 L朊病毒呈现可变或几乎不变的构象;然而，当通过大脑时，所有都变得可变。因此，突变性是一种底物特异性属性。
Murine prions transferred from brain to cultured cells gradually adapt to the new environment. Brain-derived 22L prions can infect neuroblastoma-derived PK1 cells in the presence of swainsonine (swa); that is, they are ‘swa resistant’. PK1 cell-adapted 22L prions are swa sensitive; however, propagation in swa results in selection of swa-resistant substrains. Cloned, PK1 cell-adapted 22L prions were initially unable to develop swa resistance (‘swa incompetent’); however, after serial propagation for 30–90 doublings, four of nine clones became swa competent, showing that swa-resistant ‘mutants’ arose during replication. Mutations in the case of prions are attributed to heritable changes in PrPSc conformation. One clone remained swa incompetent even after 1035-fold expansion; surprisingly, after propagation in brain, it yielded swa-resistant prions, indistinguishable from the original 22L population. Thus, cell-adapted 22L prions assumed either mutable or virtually immutable conformations; however, when passaged through the brain all became mutable. Mutability is thus a substrain-specific attribute.
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影响因子：
14.8
作者：
Roberts BE;Duennwald ML;Wang H;Chung C;Lopreiato NP;Sweeny EA;Knight MN;Shorter J
通讯作者：
Shorter J
DOI：
10.1073/pnas.0710054104
发表时间：
2007-12-26
影响因子：
11.1
作者：
Mahal, Sukhvir P.;Baker, Christopher A.;Weissmann, Charles
通讯作者：
Weissmann, Charles
影响因子：
8
作者：
Peretz, D;Scott, MR;Prusiner, SB
通讯作者：
Prusiner, SB
影响因子：
--
作者：
Shorter J
通讯作者：
Shorter J
影响因子：
6.7
作者：
Ghaemmaghami S;Ahn M;Lessard P;Giles K;Legname G;DeArmond SJ;Prusiner SB
通讯作者：
Prusiner SB