Interaction of human laminin receptor with Sup35, the [PSI⁺] prion-forming protein from S. cerevisiae: a yeast model for studies of LamR interactions with amyloidogenic proteins.
Interaction of human laminin receptor with Sup35, the [PSI⁺] prion-forming protein from S. cerevisiae: a yeast model for studies of LamR interactions with amyloidogenic proteins.
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DOI：
10.1371/journal.pone.0086013
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Meruelo D
中科院分区：
文献类型：
--
作者：
Pampeno C;Derkatch IL;Meruelo D
层粘连蛋白受体（LamR）是细胞外基质层粘连蛋白的细胞表面受体，而细胞内的相同蛋白质与核糖体、核蛋白和细胞骨架纤维相互作用。LamR已被证明是几种细菌和病毒的受体。此外，LamR与细胞和感染形式的朊病毒蛋白PrPC和PrPSc相互作用。事实上，LamR是PrPC的受体。LamR是否仅以PrP受体的能力与PrPSc相互作用，或LamR特异性识别PrPSc的朊病毒决定簇，尚不清楚。为了探索LamR是否有与朊病毒和淀粉样蛋白相互作用的倾向，我们研究了LamR与酵母朊病毒形成蛋白Sup 35的相互作用。Sup 35是一个翻译终止因子，与PrP没有同源性或功能关系。将表达LamR或与绿色荧光蛋白（GFP）融合的LamR的质粒转化到酵母菌株变体中，所述酵母菌株变体的差异在于是否存在Sup 35的朊病毒构象，分别为[PSI +]和[psi-]。通过免疫沉淀、离心分离和荧光显微镜分析揭示了[PSI +]菌株中LamR和Sup 35之间的相互作用。[PSI +]的存在促进LamR与Sup 35的共沉淀以及LamR聚集。在[PSI +]细胞中，用GFP或mCherry标记的LamR形成与可见[PSI +]焦点共定位的明亮荧光聚集体。酵母朊病毒模型将有助于在一个安全和易于操作的系统中研究LamR与淀粉样蛋白朊病毒的相互作用，这可能会导致更好地理解和治疗淀粉样蛋白疾病。
The laminin receptor (LamR) is a cell surface receptor for extracellular matrix laminin, whereas the same protein within the cell interacts with ribosomes, nuclear proteins and cytoskeletal fibers. LamR has been shown to be a receptor for several bacteria and viruses. Furthermore, LamR interacts with both cellular and infectious forms of the prion protein, PrPC and PrPSc. Indeed, LamR is a receptor for PrPC. Whether LamR interacts with PrPSc exclusively in a capacity of the PrP receptor, or LamR specifically recognizes prion determinants of PrPSc, is unclear. In order to explore whether LamR has a propensity to interact with prions and amyloids, we examined LamR interaction with the yeast prion-forming protein, Sup35. Sup35 is a translation termination factor with no homology or functional relationship to PrP. Plasmids expressing LamR or LamR fused with the green fluorescent protein (GFP) were transformed into yeast strain variants differing by the presence or absence of the prion conformation of Sup35, respectively [PSI +] and [psi −]. Analyses by immunoprecipitation, centrifugal fractionation and fluorescent microscopy reveal interaction between LamR and Sup35 in [PSI +] strains. The presence of [PSI +] promotes LamR co-precipitation with Sup35 as well as LamR aggregation. In [PSI +] cells, LamR tagged with GFP or mCherry forms bright fluorescent aggregates that co-localize with visible [PSI +] foci. The yeast prion model will facilitate studying the interaction of LamR with amyloidogenic prions in a safe and easily manipulated system that may lead to a better understanding and treatment of amyloid diseases.
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