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J Cell Biol. 2016 Jul 18;214(2):197-213. doi: 10.1083/jcb.201601025. Epub 2016 Jul 11.

Cortactin promotes exosome secretion by controlling branched actin dynamics.

Author information

1
Department of Cancer Biology, Vanderbilt University Medical School, Nashville, TN 37232.
2
Kanagawa Cancer Center, Yokohama 241-0815, Japan.
3
Department of Cell and Developmental Biology, Vanderbilt University Medical School, Nashville, TN 37232.
4
Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
5
Department of Cancer Biology, Vanderbilt University Medical School, Nashville, TN 37232 Department of Cell and Developmental Biology, Vanderbilt University Medical School, Nashville, TN 37232 Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232 alissa.weaver@vanderbilt.edu.

Abstract

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.

PMID:
27402952
PMCID:
PMC4949450
DOI:
10.1083/jcb.201601025
[Indexed for MEDLINE]
Free PMC Article

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