RAB5c coordinates early endosome-to-phagosome trafficking to drive LC3-associated phagocytosis and pathogen killing in macrophages.
New paper out in @ScienceAdvances 🧵
@pablo_jack I see. It depends a lot on your protocol, too! It’s fixed samples. In this case, there isn't a spinning disk, so it wasn't good to test on live samples.
How does the V-ATPase transmembrane core reach the phagosome during LAP (LC3 associated phagocytosis)?
Live imaging shows V0 transfer occurs via contact between V0+ organelles and the phagosome membrane, a step controlled by RAB5c+ early endosomes.
*STELLARIS Confocal Microscope
@pablo_jack We used Leica Lightning adaptive deconvolution with a theoretical PSF calculated from the optical parameters (NA 1.40, 63x oil objective, emission wavelengths 505 nm and 619 nm, 0.663 AU pinhole). The algorithm used Good's Roughness regularization (λ=0.05)
Interesting observation on V-ATPase transmembrane core and its integration during LAP via V0 transfer. The role of RAB5c+ early endosomes is indeed crucial here. Do we know how these early endosomes are initially targeted to the phagosome or the specific signals involved? Additionally, what implications might this have for understanding diseases related to phagosome-lysosome fusion defects? For more in-depth insights and related discussions on such complex biomedical queries, you might find Sci-Quest helpful, especially as it generates biomedical reviews. Feel free to explore more here: https://t.co/4Y9Imt8uIJ. #BiomedicalResearch #CellBiology #Medicine
Notably, RAB5c and V0 show no stable direct interaction, indicating V0 is delivered to phagosomes through EE trafficking rather than as a RAB5c effector.
#FluorescenceMicroscopy#LeicaMicrosystems#Lightning
A follow-up on one of the more unexpected findings from our recent @ScienceAdvances paper: RAB5c-dependent trafficking of the V-ATPase V0 sector to phagosomes. 🧵
This identifies a selective endosome-to-phagosome trafficking route as a regulatory node for LAP, and raises RAB5c as a potential target in contexts where LAP is defective or exploited by pathogens.
We show that RAB5c, an early endosome GTPase, controls V0 phagosomal delivery. Without RAB5c, V0 fails to accumulate at the phagosome, as a consequence, ATG16L1 recruitment is abrogated and LC3 conjugation does not occur!
The V-ATPase–ATG16L1 interaction is established as a trigger for non-canonical LC3 lipidation on single-membrane vesicles. What hasn't been clear is how the V0 transmembrane subunit gets to the phagosome in the first place.
RAB5c coordinates early endosome-to-phagosome trafficking to drive LC3-associated phagocytosis and pathogen killing in macrophages.
New paper out in @ScienceAdvances 🧵
Spotlight: new work from Zhao et al. (https://t.co/46J4RsIbwp) establishes a direct link between PI(3)P and #actin in mitochondrial dynamics. Sneha Hegde and Marc Germain @UQTR discuss the findings: https://t.co/M6j8htSNRp
#Mitochondria#Lipids
How RAB5C enzyme regulates the microbicidal phagosome in macrophages
📷 Edismauro Garcia Freitas-Filho et al, Universidade de São Paulo, Brazil in @ScienceAdvances
➡️ https://t.co/fEZgRDCEse
RAB5c coordinates early endosome-to-phagosome trafficking to drive LC3-associated phagocytosis and pathogen killing in macrophages.
New paper out in @ScienceAdvances 🧵