fig3

Figure 3. Mechanisms of extracellular vesicle uptake and receptor-mediated signaling in recipient cells: (1) lipid raft-dependent internalization; (2) receptor-mediated endocytosis; and (3) receptor-mediated signaling. Orange arrows indicate lipid raft-dependent internalization; blue-gray arrows indicate the illustrated EV-cell interactions, uptake, cargo release, and signaling. The dashed curved arrow indicates the illustrated uptake route toward the endosomal compartment, while thick black lines separate the three mechanisms. Integrin subunits are designated by Greek letters and numbers. Ca²⁺: Calcium ion; CXCR4: C-X-C motif chemokine receptor 4; FAK: focal adhesion kinase; GPI: glycosylphosphatidylinositol; HSPGs: heparan sulfate proteoglycans; ICAM-1: intercellular adhesion molecule 1; IFN-γ: interferon gamma; IFNGR1: interferon gamma receptor 1; LFA-1: lymphocyte function-associated antigen 1; MAdCAM-1: mucosal addressin cell adhesion molecule 1; p38: p38 mitogen-activated protein kinase; pERK: phosphorylated extracellular signal-regulated kinase; SFK: Src family kinase; STAT1: signal transducer and activator of transcription 1; Tim4: T-cell immunoglobulin and mucin domain-containing protein 4; TSPAN8: tetraspanin-8; VCAM-1: vascular cell adhesion molecule 1.