Direct recruitment of H+-ATPase from lysosomes for phagosomal acidification

Sun‐Wada, Ge‐Hong; Tabata, Hiroyuki; Kawamura, Nobuyuki; Aoyama, Minako; Wada, Yoh

doi:10.1242/jcs.050443

Cited by 141 publications

(126 citation statements)

References 51 publications

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“…Embryonic stem cell-mediated gene targeting was used to generate mice in which an a3 subunit-GFP fusion protein is expressed under the original promoter of the a3 subunit (a3-GFP mice) (13). Using bone tissue sections from these mice, we confirmed that tartrate-resistant acid phosphatase-positive (TRAPpositive) mature osteoclasts express GFP (Supplemental Figure 1C).…”

Section: Resultsmentioning

confidence: 74%

Dynamic visualization of RANKL and Th17-mediated osteoclast function

et al. 2013

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Osteoclasts are bone resorbing, multinucleate cells that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursor cells. Although previous studies have revealed important molecular signals, how the bone resorptive functions of such cells are controlled in vivo remains less well characterized. Here, we visualized fluorescently labeled mature osteoclasts in intact mouse bone tissues using intravital multiphoton microscopy. Within this mature population, we observed cells with distinct motility behaviors and function, with the relative proportion of static -bone resorptive (R) to moving -nonresorptive (N) varying in accordance with the pathophysiological conditions of the bone. We also found that rapid application of the osteoclast-activation factor RANKL converted many N osteoclasts to R, suggesting a novel point of action in RANKL-mediated control of mature osteoclast function. Furthermore, we showed that Th17 cells, a subset of RANKL-expressing CD4 + T cells, could induce rapid N-to-R conversion of mature osteoclasts via cell-cell contact. These findings provide new insights into the activities of mature osteoclasts in situ and identify actions of RANKL-expressing Th17 cells in inflammatory bone destruction.

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Section: Resultsmentioning

confidence: 74%

Dynamic visualization of RANKL and Th17-mediated osteoclast function

et al. 2013

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“…Previous studies revealed that phagosomal acidification starts early during phagosome formation, before acquisition of lysosomal features such as LAMP-1 and cathepsins (8,53,54), which are recruited to phagosomes through distinct kinetics and mechanisms (7,35,55). Recently, it was shown that early recruitment of the a3 subunit of the v-ATPase to young phagosomes occurs via tubular structures extending from the perinuclear lysosomes along microtubules (56). This finding is consistent with previous studies showing that phagosomes acquire lysosomal features through a microtubuledependent mechanism (47,50).…”

Section: Discussionmentioning

confidence: 99%

The Protein Tyrosine Phosphatase SHP-1 Regulates Phagolysosome Biogenesis

Gómez

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Duplay

et al. 2012

The Journal of Immunology

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The process of phagocytosis and phagosome maturation involves the recruitment of effector proteins that participate in phagosome formation and in the acidification and/or fusion with various endocytic vesicles. In the current study, we investigated the role of the Src homology region 2 domain-containing phosphatase 1 (SHP-1) in phagolysosome biogenesis. To this end, we used immortalized bone marrow macrophages derived from SHP-1–deficient motheaten mice and their wild-type littermates. We found that SHP-1 is recruited early and remains present on phagosomes for up to 4 h postphagocytosis. Using confocal immunofluorescence microscopy and Western blot analyses on purified phagosome extracts, we observed an impaired recruitment of lysosomal-associated membrane protein 1 in SHP-1–deficient macrophages. Moreover, Western blot analyses revealed that whereas the 51-kDa procathepsin D is recruited to phagosomes, it is not processed into the 46-kDa cathepsin D in the absence of SHP-1, suggesting a defect in acidification. Using the lysosomotropic agent LysoTracker as an indicator of phagosomal pH, we obtained evidence that in the absence of SHP-1, phagosome acidification was impaired. Taken together, these results are consistent with a role for SHP-1 in the regulation of signaling or membrane fusion events involved in phagolysosome biogenesis.

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“…An essential step during the degradation of autophagy substrates is the formation of autolysosomes upon fusion between the autophagosomes and the lysosomes and the activation of hydrolases upon acidification (Sun-Wada et al, 2009). Interestingly, LC3…”

Section: Introductionmentioning

confidence: 99%

Sperm-inherited organelle clearance inC. elegansrelies on LC3-dependent autophagosome targeting to the pericentrosomal area

et al. 2015

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Macroautophagic degradation of sperm-inherited organelles prevents paternal mitochondrial DNA transmission in C. elegans. The recruitment of autophagy markers around sperm mitochondria has also been observed in mouse and fly embryos but their role in degradation is debated. Both worm Atg8 ubiquitin-like proteins, LGG-1/GABARAP and LGG-2/LC3, are recruited around sperm organelles after fertilization. Whereas LGG-1 depletion affects autophagosome function, stabilizes the substrates and is lethal, we demonstrate that LGG-2 is dispensable for autophagosome formation but participates in their microtubule-dependent transport toward the pericentrosomal area prior to acidification. In the absence of LGG-2, autophagosomes and their substrates remain clustered at the cell cortex, away from the centrosomes and their associated lysosomes. Thus, the clearance of sperm organelles is delayed and their segregation between blastomeres prevented. This allowed us to reveal a role of the RAB-5/RAB-7 GTPases in autophagosome formation. In conclusion, the major contribution of LGG-2 in sperm-inherited organelle clearance resides in its capacity to mediate the retrograde transport of autophagosomes rather than their fusion with acidic compartments: a potential key function of LC3 in controlling the fate of sperm mitochondria in other species.

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Direct recruitment of H+-ATPase from lysosomes for phagosomal acidification

Cited by 141 publications

References 51 publications

Dynamic visualization of RANKL and Th17-mediated osteoclast function

Dynamic visualization of RANKL and Th17-mediated osteoclast function

The Protein Tyrosine Phosphatase SHP-1 Regulates Phagolysosome Biogenesis

Sperm-inherited organelle clearance inC. elegansrelies on LC3-dependent autophagosome targeting to the pericentrosomal area

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