@article{676a8e48b7414e769c46df9fa20e4a0b,
title = "Extracellular vesicles direct migration by synthesizing and releasing chemotactic signals",
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 D. discoideum cells are functional entities that mediate signal relay during chemotaxis and streaming.",
author = "Kriebel, {Paul W.} and Ritankar Majumdar and Jenkins, {Lisa M.} and Hiroshi Senoo and Weiye Wang and Sonia Ammu and Song Chen and Kedar Narayan and Miho Iijima and Parent, {Carole A.}",
note = "Funding Information: 1Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; 2Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; 3Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; 4Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD; 5Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD; 6Department of Pharmacology, University of Michigan, Ann Arbor, MI; 7Institute for Physical Science and Technology, University of Maryland, College Park, MD. Funding Information: This work was supported in whole or in part with federal funds from the National Cancer Institute (NIH) to C.A. Parent and under contract no. HHSN261200800001E to K. Narayan as well as by NIH grant R01GM084015 to M. Iijima. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. The authors declare no competing financial interests.",
year = "2018",
month = aug,
day = "1",
doi = "10.1083/jcb.201710170",
language = "English (US)",
volume = "217",
pages = "2891--2910",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "8",
}