Uptake of small extracellular vesicles by recipient cells is facilitated by paracrine adhesion signaling

• DOI: 10.1038/s41467-025-57617-9
• Publication Date: 2025-03-12T10:05:08Z
• Authors: Koichiro M. Hirosawa; Yusuke Sato; Rinshi S. Kasai; Eriko Yamaguchi; Naoko Komura; Hiromune Ando; Ayuko Hoshino; Yasunari Yokota; Kenichi G. N. Suzuki
• Keywords: Internalization; Juxtacrine signalling

Abstract Small extracellular vesicles (sEVs) play crucial roles in intercellular communication. However, the internalization of individual sEVs by recipient cells has not been directly observed. Here, we examined these mechanisms using state-of-the-art imaging techniques. Single-molecule shows that tumor-derived can be classified into several subtypes. Simultaneous single-sEV particle tracking and observation super-resolution movies membrane invaginations living reveal all sEV subtypes are internalized via clathrin-independent endocytosis mediated galectin-3 lysosome-associated protein-2C, while some recruited raft markers through caveolae. Integrin β1 talin-1 accumulate cell plasma membranes beneath Paracrine, but autocrine, binding triggers Ca 2+ mobilization induced activation Src family kinases phospholipase Cγ. Subsequent -induced calcineurin–dynamin promotes internalization, leading to recycling pathway. Thus, clarified detailed driven paracrine adhesion signaling.