School of Chemistry and Molecular Biosciences, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia; Molecular Horizons Research Institute, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia.
School of Chemistry and Molecular Biosciences, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia; Molecular Horizons Research Institute, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia; Illawarra Health and Medical Research Institute, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia.
Trends Biochem Sci. 2021 Aug;46(8):652-660. doi: 10.1016/j.tibs.2021.01.005. Epub 2021 Feb 9.
Clusterin (CLU) was the first reported secreted mammalian chaperone and impacts on serious diseases associated with inappropriate extracellular protein aggregation. Many studies have described intracellular CLU in locations outside the secretory system and recent work has shown that CLU can be released into the cytosol during cell stress. In this article, we critically evaluate evidence relevant to the proposed origins of cellular CLU found outside the secretory system, and advance the hypothesis that the cytosolic release of CLU induced by stress serves to facilitate the trafficking of misfolded proteins to the proteasome and autophagy for degradation. We also propose future research directions that could help establish CLU as a unique chaperone performing critical and synergic roles in both intracellular and extracellular proteostasis.
簇集蛋白 (CLU) 是第一个被报道的分泌性哺乳动物伴侣蛋白，它与不适当的细胞外蛋白聚集相关的严重疾病有关。许多研究已经描述了细胞内 CLU 在分泌系统之外的位置，最近的工作表明，CLU 在细胞应激时可以释放到细胞质中。在本文中，我们批判性地评估了与提出的细胞外分泌系统外 CLU 起源相关的证据，并提出了这样一种假设，即应激诱导的 CLU 细胞质释放有助于促进错误折叠蛋白向蛋白酶体和自噬体的运输，以进行降解。我们还提出了未来的研究方向，这可能有助于确立 CLU 作为一种独特的伴侣蛋白，在细胞内和细胞外蛋白质稳态中发挥关键和协同作用。
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