Circadian regulation of protein cargo in extracellular vesicles

Ching-Yan Chloé Yeung, Frank Dondelinger, Erwin M Schoof, Birgitte Georg, Yinhui Lu, Zhiyong Zheng, Jingdong Zhang, Jens Hannibal, Jan Fahrenkrug, Michael Kjaer


The circadian clock controls many aspects of physiology, but it remains undescribed whether extracellular vesicles (EVs), including exosomes, involved in cell-cell communications between tissues are regulated in a circadian pattern. We demonstrate a 24-hour rhythmic abundance of individual proteins in small EVs using liquid chromatography-mass spectrometry in circadian-synchronized tendon fibroblasts. Furthermore, the release of small EVs enriched in RNA binding proteins was temporally separated from those enriched in cytoskeletal and matrix proteins, which peaked during the end of the light phase. Last, we targeted the protein sorting mechanism in the exosome biogenesis pathway and established (by knockdown of circadian-regulated flotillin-1) that matrix metalloproteinase 14 abundance in tendon fibroblast small EVs is under flotillin-1 regulation. In conclusion, we have identified proteomic time signatures for small EVs released by tendon fibroblasts, which supports the view that the circadian clock regulates protein cargo in EVs involved in cell-cell cross-talk.

Original languageEnglish
Article numbereabc9061
JournalScience Advances
Issue number14
Pages (from-to)eabc9061
Publication statusPublished - 8 Apr 2022


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