Cortactin promotes exosome secretion by controlling branched actin dynamics.

Sinha S, Hoshino D, Hong NH, Kirkbride KC, Grega-Larson NE, Seiki M, Tyska MJ, Weaver AM
J Cell Biol. 2016 214 (2): 197-213

PMID: 27402952 · PMCID: PMC4949450 · DOI:10.1083/jcb.201601025

Exosomes are extracellular vesicles that influence cellular behavior and enhance cancer aggressiveness by carrying bioactive molecules. The mechanisms that regulate exosome secretion are poorly understood. Here, we show that the actin cytoskeletal regulatory protein cortactin promotes exosome secretion. Knockdown or overexpression of cortactin in cancer cells leads to a respective decrease or increase in exosome secretion, without altering exosome cargo content. Live-cell imaging revealed that cortactin controls both trafficking and plasma membrane docking of multivesicular late endosomes (MVEs). Regulation of exosome secretion by cortactin requires binding to the branched actin nucleating Arp2/3 complex and to actin filaments. Furthermore, cortactin, Rab27a, and coronin 1b coordinately control stability of cortical actin MVE docking sites and exosome secretion. Functionally, the addition of purified exosomes to cortactin-knockdown cells rescued defects of those cells in serum-independent growth and invasion. These data suggest a model in which cortactin promotes exosome secretion by stabilizing cortical actin-rich MVE docking sites.

© 2016 Sinha et al.

MeSH Terms (18)

Actin-Related Protein 2-3 Complex Actins Biological Transport Cell Line, Tumor Cell Membrane Cortactin Exosomes Humans Microfilament Proteins Models, Biological Molecular Docking Simulation Multivesicular Bodies Phenotype Protein Binding Pseudopodia rab GTP-Binding Proteins RNA, Small Interfering Tetraspanin 30

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