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

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 imaging shows that tumor-derived sEVs can be classified into several subtypes. Simultaneous single-sEV particle tracking and observation of super-resolution movies of membrane invaginations in living cells reveal that all sEV subtypes are internalized via clathrin-independent endocytosis mediated by galectin-3 and lysosome-associated membrane protein-2C, while some subtypes that recruited raft markers are internalized through…

• TS
  Takeda Science Foundation
• UM
  Uehara Memorial Foundation
• JA
  Japan Agency for Medical Research and Development

  Award: 23tk0124003h001, 1268282
• JS
  Japan Society for the Promotion of Science

  Awards: JPJSCCA202000007, 20K21387,20K21387,JPJSCCA202000007
• JS
  Japan Science and Technology Agency

  Award: JPMJFR216B
• CR
  Core Research for Evolutional Science and Technology

  Awards: JPMJCR24B3, JPMJCR18H2
• PR
  Precursory Research for Embryonic Science and Technology

  Awards: JPMJPR19H4, JPMJPR18H9