Cell type-selective secretome profiling in vivo

Autor: Wei Wei, Jonathan Z. Long, Andrew C. Yang, Veronica L. Li, Joon T. Kim, Carolyn R. Bertozzi, Nicholas M. Riley, Stephanie M. Terrell, Marta Garcia-Contreras
Rok vydání: 2020
Předmět:
Zdroj: Nature chemical biology
ISSN: 1552-4469
1552-4450
Popis: Secreted polypeptides are a fundamental axis of intercellular and endocrine communication. However, a global understanding of the composition and dynamics of cellular secretomes in intact mammalian organisms has been lacking. Here, we introduce a proximity biotinylation strategy that enables labeling, detection and enrichment of secreted polypeptides in a cell type-selective manner in mice. We generate a proteomic atlas of hepatocyte, myocyte, pericyte and myeloid cell secretomes by direct purification of biotinylated secreted proteins from blood plasma. Our secretome dataset validates known cell type-protein pairs, reveals secreted polypeptides that distinguish between cell types and identifies new cellular sources for classical plasma proteins. Lastly, we uncover a dynamic and previously undescribed nutrient-dependent reprogramming of the hepatocyte secretome characterized by the increased unconventional secretion of the cytosolic enzyme betaine-homocysteine S-methyltransferase (BHMT). This secretome profiling strategy enables dynamic and cell type-specific dissection of the plasma proteome and the secreted polypeptides that mediate intercellular signaling.
Databáze: OpenAIRE