Phase separation of α-crystallin-GFP protein and its implication in cataract disease.

Autor: Shi J; Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China., Zhu YX; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.; Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China., Huang RY; Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China., Bai SM; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.; Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China., Zheng YX; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.; Department of Ophthalmology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China., Zheng J; Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China., Xia ZX; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China. xiazhaox@mail.sysu.edu.cn.; Department of Ophthalmology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China. xiazhaox@mail.sysu.edu.cn., Wang YL; Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China. wangylong7@mail.sysu.edu.cn.; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China. wangylong7@mail.sysu.edu.cn.; Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China. wangylong7@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Mar 24; Vol. 13 (1), pp. 4832. Date of Electronic Publication: 2023 Mar 24.
DOI: 10.1038/s41598-023-31845-9
Abstrakt: Cataract, the leading cause of blindness worldwide, is caused by crystallin protein aggregation within the protected lens environment. Phase separation has been implicated as an important mechanism of protein aggregation diseases, such as neurodegeneration. Similarly, cataract has been proposed to be a protein condensation disease in the last century. However, whether crystallin proteins aggregate via a phase separation mechanism and which crystallin protein initiates the aggregation remain unclear. Here, we showed that all types of crystallin-GFP proteins remain soluble under physiological conditions, including protein concentrations, ion strength, and crowding environments. However, in age or disease-induced aberrant conditions, α-crystallin-GFP, including αA- and αB-crystallin-GFP, but not other crystallin-GFP proteins, undergo phase separation in vivo and in vitro. We found that aging-related changes, including higher crystallin concentrations, increased Na + , and decreased K + concentrations, induced the aggregation of α-crystallin-GFP. Furthermore, H 2 O 2 , glucose, and sorbitol, the well-known risk factors for cataract, significantly enhanced the aggregation of αB-crystallin-GFP. Taken together, our results revealed that α-crystallin-GFP forms aggregates via a phase transition process, which may play roles in cataract disease. Opposite to the previously reported function of enhancing the solubility of other crystallin, α-crystallin may be the major aggregated crystallin in the lens of cataract patients.
(© 2023. The Author(s).)
Databáze: MEDLINE
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