Cell News 01/2017
28
Determining the fate of extracellular vesicles in C. elegans:
trafficking of released organelles
Gholamreza Fazeli, Michaela Geisenhof, Linda Irmisch, and Ann M Wehman
Presenting author: Ann Wehman
Rudolf-Virchow-Zentrum der Universität Würzburg
The fate of most extracellular vesicles (EV) is unclear due to
their small size. In addition to EVs, animal cells also release
organelles. For example, the midbody coordinates the end of
cytokinesis, when two daughter cells separate through an
intercellular bridge. At abscission, the midbody remnant is
released extracellularly by cuts on both sides of the bridge.
Released midbody vesicles can be found in body fluids, but are
often phagocytosed in vivo. To determine the fate of mid-
bodies, we examined the role of phagocytic, endosomal, and
autophagic proteins on individual midbodies in developing C.
elegans embryos.
We first confirmed that midbodies are released in 1 µm
vesicles using the ZF1 degradation tag to label extracellular
vesicle membranes. Released midbodies are internalized via
actin-driven phagocytosis, which requires the RAB-5 GTPase to
localize the Class III Phosphoinositide 3-Kinase (PI3K) complex
at the cortex, leading to recycling of the phagocytic receptor
CED-1 to the plasma membrane. Further, we found that RAB-5
and RAB-7 appear on midbody phagosomes, directing their
maturation similar to endosomes. Proteins normally associated
with macroautophagy, such as the Atg8/LC3 homologs LGG-1
and LGG-2, localize around the midbody phagosome and are
required for midbody degradation. Additionally, we observed
that the Rab2 homolog UNC-108 is required for acidification
of the midbody phagosome, demonstrating that LC3-associ-
ated phagosomes (LAPosomes) acidify via a common pathway
with classical phagosomes.
These studies reveal that internalized midbody remnants are
degraded via LC3-associated phagocytosis (LAP). Phagocytosis
of midbodies likely terminates midbody signaling after their
release. After phagocytosis, the recruitment of LC3 to the
phagosome may be necessary for the degradation of a double
membrane-wrapped phagosome. Thus, the fate of the midbody
reveals how cells cope with released extracellular organelles,
likely to be similar to the fate of EVs.
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