Cellular internalization of exosomes occurs through phagocytosis.
Exosomes play important roles in many physiological and pathological processes. However, the exosome-cell interaction mode and the intracellular trafficking pathway of exosomes in their recipient cells remain unclear. Here, we report that exosomes derived from K562 or MT4 cells are internalized more efficiently by phagocytes than by non-phagocytic cells. Most exosomes were observed attached to the plasma membrane of non-phagocytic cells, while in phagocytic cells these exosomes were found to enter via phagocytosis. Specifically, they moved to phagosomes together with phagocytic polystyrene carboxylate-modified latex beads (biospheres) and were further sorted into phagolysosomes. Moreover, exosome internalization was dependent on the actin cytoskeleton and phosphatidylinositol 3-kinase, and could be inhibited by the knockdown of dynamin2 or overexpression of a dominant-negative form of dynamin2. Further, antibody pretreatment assays demonstrated that tim4 but not tim1 was involved in exosomes uptake. We also found that exosomes did not enter the internalization pathway involving caveolae, macropinocytosis and clathrin-coated vesicles. Our observation that the cellular uptake of exosomes occurs through phagocytosis has important implications for exosome-cell interactions and the exosome intracellular trafficking pathway.
Feng
Du
D
School of Life Sciences, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing, PR China.
Zhao
Wen-Long
WL
Ye
Yun-Ying
YY
Bai
Xiao-Chen
XC
Liu
Rui-Qin
RQ
Chang
Lei-Fu
LF
Zhou
Qiang
Q
Sui
Sen-Fang
SF
D001692:Biological Transport; D021941:Caveolae / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002477:Cells / Q000378:metabolism; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport
D019869:Phosphatidylinositol 3-Kinases