Dynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice

Cited 23 time in Web of Science Cited 25 time in Scopus

Kim, Kwang-eun; Park, Isaac; Kim, Jeesoo; Kang, Myeong-Gyun; Choi, Won Gun; Shin, Hyemi; Kim, Jong-Seo; Rhee, Hyun-Woo; Suh, Jae Myoung

Issue Date
Nature Publishing Group
Nature Communications, Vol.12 No.1, p. 5204
Secretory proteins are an essential component of interorgan communication networks that regulate animal physiology. Current approaches for identifying secretory proteins from specific cell and tissue types are largely limited to in vitro or ex vivo models which often fail to recapitulate in vivo biology. As such, there is mounting interest in developing in vivo analytical tools that can provide accurate information on the origin, identity, and spatiotemporal dynamics of secretory proteins. Here, we describe iSLET (in situ Secretory protein Labeling via ER-anchored TurboID) which selectively labels proteins that transit through the classical secretory pathway via catalytic actions of Sec61b-TurboID, a proximity labeling enzyme anchored in the ER lumen. To validate iSLET in a whole-body system, we express iSLET in the mouse liver and demonstrate efficient labeling of liver secretory proteins which could be tracked and identified within circulating blood plasma. Furthermore, proteomic analysis of the labeled liver secretome enriched from liver iSLET mouse plasma is highly consistent with previous reports of liver secretory protein profiles. Taken together, iSLET is a versatile and powerful tool for studying spatiotemporal dynamics of secretory proteins, a valuable class of biomarkers and therapeutic targets. The in vivo identification of proteins secreted from a specific cell type or tissue remains challenging. Here, the authors develop a proximity labeling-based method to selectively label secreted proteins and combine it with proteomics to identify liver secretory proteins in mouse plasma.
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
College of Natural Sciences (자연과학대학)Dept. of Chemistry (화학부)Journal Papers (저널논문_화학부)
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