Extracellular vesicles direct migration by synthesizing and releasing chemotactic signals

Paul W. Kriebel, Ritankar Majumdar, Lisa M. Jenkins, Hiroshi Senoo, Weiye Wang, Sonia Ammu, Song Chen, Kedar Narayan, Miho Iijima, Carole A. Parent

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2891-2910
Number of pages20
JournalJournal of Cell Biology
Volume217
Issue number8
DOIs
StatePublished - Aug 1 2018

ASJC Scopus subject areas

  • Cell Biology

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