2026-06-22 ロックフェラー大学
＜関連情報＞
- https://www.rockefeller.edu/news/39962-obesity-immunity-protein-tagging/
- https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00585-1
細胞型特異的な臓器分泌タンパク質の近接標識により、エネルギーバランスに依存したタンパク質再構築が明らかになる Cell-type-specific proximity labeling of organ secretomes reveals energy balance-dependent proteomic remodeling
Kaja Plucińska ∙ Charlotte R. Wayne ∙ Henry Sanford ∙ … ∙ Ken H. Loh ∙ Paul Cohen ∙ Ekaterina V. Vinogradova
Cell Reports Published:June 11, 2026
DOI:https://doi.org/10.1016/j.celrep.2026.117507
Graphical abstract
Highlights
- Genetically encoded TurboIDKDEL enables cell-type-specific secretome labeling
- Metabolic stress alters ER proteostasis in a dynamic and cell-specific manner
- ER stress and ECM proteomes are differentially affected by energy state
- Cell-type-specific secretome labeling identifies plasma markers of human disease
Summary
Intercellular communication is critical for maintaining organismal metabolic homeostasis. Here, we develop a method enabling temporally controlled, cell-type-specific labeling of secreted and membrane proteins in key metabolic tissues. The method employs a genetically encoded proximity-labeling strategy by targeting a Cre-dependent TurboID ligase to the endoplasmic reticulum (ER) in ES cell-derived mice. The expression of TurboID in hepatocytes, adipocytes, and B lymphocytes enabled the characterization of cell type-specific ER proteomes at baseline and in response to fasting, inflammation, and dietary obesity, revealing tissue- and perturbation-specific changes and augmenting our understanding of how the proteomes of individual tissues change to regulate systemic energy balance. This comprehensive resource represents an important advance toward understanding both how cell-to-cell communication changes in response to energy balance and how it contributes to these alterations. This method is broadly applicable and provides a means for identifying biomarkers and therapeutic targets across a wide range of tissues.
