The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
J Biol Chem. 2011 Jan 7;286(1):726-36. doi: 10.1074/jbc.M110.177352. Epub 2010 Oct 18.
Molecular chaperones and co-chaperones are crucial for cellular development and maintenance as they assist in protein folding and stabilization of unfolded or misfolded proteins. Prefoldin (PFDN), a ubiquitously expressed heterohexameric co-chaperone, is necessary for proper folding of nascent proteins, in particular, tubulin and actin. Here we show that a genetic disruption in the murine Pfdn5 gene, a subunit of prefoldin, causes a syndrome characterized by photoreceptor degeneration, central nervous system abnormalities, and male infertility. Our data indicate that a missense mutation in Pfdn5, may cause these phenotypes through a reduction in formation of microtubules and microfilaments, which are necessary for the development of cilia and cytoskeletal structures, respectively. The diversity of phenotypes demonstrated by models carrying mutations in different PFDN subunits suggests that each PFDN subunit must confer a distinct substrate specificity to the prefoldin holocomplex.
分子伴侣和共伴侣对于细胞的发育和维持至关重要，因为它们有助于蛋白质的折叠和未折叠或错误折叠蛋白质的稳定。Prefoldin（PFDN）是一种广泛表达的异六聚体共伴侣，对于新生蛋白质，特别是微管蛋白和肌动蛋白的正确折叠是必需的。在这里，我们展示了小鼠 Pfdn5 基因（prefoldin 的一个亚基）的遗传破坏会导致一种综合征，其特征是感光器退化、中枢神经系统异常和男性不育。我们的数据表明，Pfdn5 中的错义突变可能通过减少微管和微丝的形成导致这些表型，微管和微丝分别是纤毛和细胞骨架结构发育所必需的。携带不同 PFDN 亚基突变的模型表现出的表型多样性表明，每个 PFDN 亚基都必须赋予 prefolding 全复合物独特的底物特异性。
