Xiaoqiong Wei, PhD (left) and Liangguang (Leo) Lin, PhD
Researchers in the Department of Molecular Physiology and Biological Physics at UVA have made a significant stride in understanding the intricate workings of endoplasmic reticulum-associated degradation (ERAD), a principal protein quality-control mechanism in the ER. In a recent study published in Nature Communications, a team led by Xiaoqiong Wei, PhD, You Lu, PhD, and Liangguang Leo Lin, PhD, in the Ling Qi laboratory, has identified more than 100 endogenous ERAD substrates.
ERAD is an essential protein quality control machinery in the endoplasmic reticulum, that regulates protein abundance and biogenesis as well as organellar crosstalk; however, the nature of its endogenous substrates remains largely unknown. SEL1L-HRD1 protein complex represents the most conserved ERAD branch and has been the focus of the Qi laboratory for over a decade.
Employing a novel immunoprecipitation-based proteomic screening approach, the team uncovered over 100 high-confidence potential SEL1L-HRD1 ERAD substrates both in vitro (HEK293T cells) and in vivo (mouse brown adipose tissue), offers an invaluable resource for the scientific community. Moreover, the researchers validated several of their findings through biochemical analyses and elucidated the critical role of the SEL1L-HRD1 ERAD complex in the function of the glycosylphosphatidylinositol (GPI) transamidase complex. GPI transamidase complex catalyzes the biogenesis of GPI-anchored proteins, many of which are involved in a number of cellular processes essential for health and disease. Hence, this study not only provides crucial insights into the physiological importance of SEL1L-HRD1 ERAD, but also presents an efficient, high-throughput methodology for the community.
This study was supported by National Institutes of Health R01DK128077, 1R01DK132068, 1R01DK120047, DK120330 and 1R35GM130292, the American Society of Nephrology Postdoctoral Fellowship and National Ataxia Foundation Post- and Pre-doctoral Fellowship.
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