Exosomes from human lymphoblastoid B cells express enzymatically active CD38 that is associated with signaling complexes containing CD81, Hsc-70 and Lyn.
Exosome vesicles of endocytic origin are involved in communication between tumor and immune cells. In addition, membrane rafts (MR) may support the sorting of proteins associated with exosomes. CD38 is found at the plasma membrane and in recycling endosomes, which are both redistributed toward the immunological synapse (IS) upon T cell antigen receptor (TCR) engagement. The data of this study provide evidence that CD38 is expressed on the surface of secreted exosomes derived from lymphoblastoid B cells. Exosomic CD38 is associated with the signaling molecules CD81, Hsc-70 and Lyn. Likewise, in MR, CD38 is associated with CD81, CD19, Lyn, Galphai-2, Hsc-70 and actin. Therefore, a high degree of overlap in the pattern of signaling proteins associated with CD38 in exosomes and MR exists. Exosomic and MR CD38, by virtue of these interactions, have signaling potential. Indeed, CD38 is enzymatically active in both exosomes and MR, and CD38 ligation induces Akt/PKB and Erk activation, which is accompanied by increased translocation of CD38 into MR. In conclusion, the present study indicates that CD38 localizes to MR, where it promotes cell signaling, and it is exported out of the cells through the exosome-mediated exocytic pathway, where it may act as an intercellular messenger.
Zumaquero
Esther
E
Dep. of Cellular Biology and Immunology, Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Armilla, Granada, Spain. ezm@ipb.csic.es
Muñoz
Pilar
P
Cobo
Marién
M
Lucena
Gema
G
Pavón
Esther J
EJ
Martín
Ana
A
Navarro
Pilar
P
García-Pérez
Angelica
A
Ariza-Veguillas
Adriana
A
Malavasi
Fabio
F
Sancho
Jaime
J
Zubiaur
Mercedes
M
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D055354:Exosomes / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D015398:Signal Transduction; D060225:Tetraspanin 28; D019061:src-Family Kinases / Q000378:metabolism*
D015703:Antigens, CD; C554798:CD81 protein, human; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D060225:Tetraspanin 28; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D051997:ADP-ribosyl Cyclase 1