Exosome Release Is Regulated by a Calcium-dependent Mechanism in K562 Cells*

By A. Savina, M. Furlán, M. Vidal, Marina Colombo. Journal of Biological Chemistry, 2003

794 citations recorded by the source corpus.

Multivesicular bodies (MVBs) are endocytic structures that contain small vesicles formed by the budding of an endosomal membrane into the lumen of the compartment. Fusion of MVBs with the plasma membrane results in secretion of the small internal vesicles termed exosomes. K562 cells are a hematopoietic cell line that releases exosomes. The application of monensin (MON) generated large MVBs that were labeled with a fluorescent lipid. Exosome release was markedly enhanced by MON treatment, a Na+/H+ exchanger that induces changes in intracellular calcium (Ca2+). To explore the possibility that the effect of MON on exosome release was caused via an increase in Ca2+, we have used a calcium ionophore and a chelator of intracellular Ca2+. Our results indicate that increasing intracellular Ca2+ stimulates exosome secretion. Furthermore, MON-stimulated exosome release was completely eliminated by 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM), implying a requirement for Ca2+ in this process. We have observed that the large MVBs generated in the presence of MON accumulated Ca2+ as determined by labeling with Fluo3-AM, suggesting that intralumenal Ca2+ might play a critical role in the secretory process. Interestingly, our results indicate that transferrin (Tf) stimulated exosome release in a Ca2+-dependent manner, suggesting that Tf might be a physiological stimulus for exosome release in K562 cells.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/492c771115e97156cbe197de76a183ebd4039b5b

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Citations in the corpus

Exosomes in cancer: small particle, big player (2015, background): “The accumulation of intracellular Ca results in increased exosome secretion [6].”
Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C (2010, methodology): “Because exosome release is known to be stimulated by intracellular Ca2+ levels (Savina et al., 2003; Krämer-Albers et al., 2007), we determined vesicular fusion after Ca2+ stimulation by whole-cell capacitance measurements (Cm; Voets, 2000).”
Cell-Produced α-Synuclein Is Secreted in a Calcium-Dependent Manner by Exosomes and Impacts Neuronal Survival (2010, background): “Exosome-mediated exocytosis is a calcium-dependent process (Raposo et al., 1997; Savina et al., 2003, 2005).”
Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake (2016, neutral): “Release of exosomes through fusion of the MVB with the plasma membrane facilitated by RAB11 and RAB35 was first found when screening with dominate-negative Rab GTPase mutants (Savina et al. 2003; Hsu et al. 2010).”
Classification, Functions, and Clinical Relevance of Extracellular Vesicles (2012, background): “, 2010) or to lysosomes for degradation (Stenmark, 2009), as well as cytosolic calcium levels (Savina et al., 2003; Fauré et al., 2006; Krämer-Albers et al., 2007), citron kinase, (Loomis et al.”
Exosomes: endosomal-derived vesicles shipping extracellular messages. (2004, background): “For mast cells and reticulocytes, it has been proposed that MVBs fuse with the cell surface in a Ca2þdependent manner [10,47].”
Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication (2013, background): “Increase in cytoplasmic Ca triggers exosome release from several cell types, including neurons and oligodendrocytes [10,21,22].”
Exosomes are released by cultured cortical neurones. (2006, result): “Our experiments are thus in good agreement with findings that exosomal release by cells of an erythroleukemic cell line is enhanced upon rising intracellular calcium levels (Raposo et al., 1997; Savina et al., 2003, 2005).”
Exosomes in Tumor Microenvironment Influence Cancer Progression and Metastasis (2013, background): “Exosome secretion is triggered by an intracellular increase of calcium (Ca) [64].”