한빛사논문, 상위피인용논문
Kwang-eun Kim1,5, Isaac Park2,5, Jeesoo Kim3,4, Myeong-Gyun Kang2, Won Gun Choi1, Hyemi Shin1, Jong-Seo Kim3,4,*, Hyun-Woo Rhee2,4,* & Jae Myoung Suh1,*
1Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea. 2Department of Chemistry, Seoul National University, Seoul, Republic of Korea. 3Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea. 4School of Biological Sciences, Seoul National University, Seoul, Republic of Korea. 5These authors contributed equally: Kwang-eun Kim, Isaac Park
*Corresponding author.
Abstract
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.
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