Abstract
Extracellular vesicles (EVs) released by cells have a role in intercellular communication to regulate a wide range of biological processes. Two types of EVs can be recognized. Exosomes, which are released from multi-vesicular bodies upon fusion with the plasma membrane, and ectosomes, which directly bud from the plasma membrane. How cells regulate the quantity of EV release is largely unknown. One of the initiating events in vesicle biogenesis is the regulated transport of phospholipids from the exoplasmic to the cytosolic leaflet of biological membranes. This process is catalyzed by P4-ATPases. The role of these phospholipid transporters in intracellular vesicle transport has been established in lower eukaryotes and is slowly emerging in mammalian cells. In Caenorhabditis elegans (C. elegans), deficiency of the P4-ATPase member TAT-5 resulted in enhanced EV shedding, indicating a role in the regulation of EV release. In this study, we investigated whether the mammalian ortholog of TAT-5, ATP9A, has a similar function in mammalian cells. We show that knockdown of ATP9A expression in human hepatoma cells resulted in a significant increase in EV release that was independent of caspase-3 activation. Pharmacological blocking of exosome release in ATP9A knockdown cells did significantly reduce the total number of EVs. Our data support a role for ATP9A in the regulation of exosome release from human cells.
Highlights
Extracellular vesicles (EVs) are carriers of a wide range of signaling molecules, including proteins, messenger- and micro-RNAs, that regulate a wide range ofphysiological processes, including blood coagulation, angiogenesis, detoxification and immune responses [1,2,3,4]
Loss of the P4-ATPase TAT-5 resulted in increased EV release from C. elegans embryos [20]
To investigate whether its mammalian ortholog ATP9A controls EV release in mammalian cells, we studied the effect of ATP9A knock-down (KD) in the human hepatoma cell line HepG2
Summary
Extracellular vesicles (EVs) are carriers of a wide range of signaling molecules, including proteins, messenger- and micro-RNAs, that regulate a wide range of (patho)physiological processes, including blood coagulation, angiogenesis, detoxification and immune responses [1,2,3,4]. Cancer cells use EVs to dictate their microenvironment to promote their proliferation and survival [5]. ATP9A in exosome release such as the transferrin receptor during the maturation of reticulocytes [6]. Drug transport by extracellular vesicles underlies multidrug resistance in cancer cells and to dispose of active caspase-3 thereby preventing apoptosis [7, 8]. Exosomes are released by fusion of multivesicular endosomes (MVEs) with the plasma membrane, whereas ectosomes are formed by direct outward budding of the plasma membrane [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
