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J Cell Biol. 2018 Aug 6;217(8):2891-2910. doi: 10.1083/jcb.201710170. Epub 2018 Jun 8.

Extracellular vesicles direct migration by synthesizing and releasing chemotactic signals.

Author information

1
Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
2
Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD ritankar@umich.edu.
3
Department of Pharmacology, University of Michigan, Ann Arbor, MI.
4
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
5
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD.
6
Institute for Physical Science and Technology, University of Maryland, College Park, MD.
7
Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
8
Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD.
9
Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD parentc@umich.edu.

Abstract

Chemotactic signals are relayed to neighboring cells through the secretion of additional chemoattractants. We previously showed in Dictyostelium discoideum that the adenylyl cyclase A, which synthesizes the chemoattractant cyclic adenosine monophosphate (cAMP), is present in the intraluminal vesicles of multivesicular bodies (MVBs) that coalesce at the back of cells. Using ultrastructural reconstructions, we now show that ACA-containing MVBs release their contents to attract neighboring cells. We show that the released vesicles are capable of directing migration and streaming and are central to chemotactic signal relay. We demonstrate that the released vesicles not only contain cAMP but also can actively synthesize and release cAMP to promote chemotaxis. Through proteomic, pharmacological, and genetic approaches, we determined that the vesicular cAMP is released via the ABCC8 transporter. Together, our findings show that extracellular vesicles released by Ddiscoideum cells are functional entities that mediate signal relay during chemotaxis and streaming.

PMID:
29884750
PMCID:
PMC6080930
DOI:
10.1083/jcb.201710170
[Indexed for MEDLINE]
Free PMC Article

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