The v-ATPase V 0 Subunit a1 Is Required for a Late Step in Synaptic Vesicle Exocytosis in Drosophila

Hiesinger, P. Robin; Fayyazuddin, Amir; Mehta, Sunil; Rosenmund, Tanja; Schulze, Karen L.; Zhai, R. Grace; Verstreken, Patrik; Cao, Yu; Zhou, Yi; Kunz, Jeannette; Bellen, Hugo J.

doi:10.1016/j.cell.2005.03.012

Cited by 284 publications

(374 citation statements)

References 49 publications

(64 reference statements)

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“…Indeed, further studies revealed that the a1 subunit of the V 0 sector is a crucial factor in vacuole fusion, acting downstream of trans-SNARE pairing (60,61). Consistently, the V 0 sector was involved in vesicle fusion during exocytosis in neurons (62,63). More recently, studies with zebrafish microglia established that the a1 subunit mediates fusion independently of its proton pump activity (64).…”

Section: Discussionmentioning

confidence: 60%

The Protein Tyrosine Phosphatase SHP-1 Regulates Phagolysosome Biogenesis

Gómez

Shio

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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Section: Discussionmentioning

confidence: 60%

The Protein Tyrosine Phosphatase SHP-1 Regulates Phagolysosome Biogenesis

Gómez

Shio

Duplay

et al. 2012

The Journal of Immunology

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“…On the other hand, the vesicle fusion and its apparatus must be more or less similar among different types of neurons [63][64][65][66][67]. In any case, however, the evidence for somatic or dendritic release of DA through ATP6V0C in non-dopaminergic neurons or glia is likely to be very weak at this moment.…”

Section: Overview Of Gene or Cell Transplantation Therapy For Neurodementioning

confidence: 99%

“…It is possible to postulate another mechanism whereby a complex of proteolipid channels involved in SNARE fusion may effectively secrete DA from DA-accumulating cells in the striatum, as described in yeast and Drosophila [7,65,66].…”

Section: Overview Of Gene or Cell Transplantation Therapy For Neurodementioning

confidence: 99%

Neurotransmitter release: vacuolar ATPase V0 sector c-subunits in possible gene or cell therapies for Parkinson’s, Alzheimer’s, and psychiatric diseases

et al. 2016

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Gene therapy or cell transplantation therapy has made great progress in recent years. We overview mediatophore as a potential medical usage for gene and transplantation therapies in the nervous system. The 16-kDa proteolipid mediatophore was shown to mediate the secretion of acetylcholine in a Ca 2+ -dependent manner. Mediatophore is known to be identical to the transmembrane c-subunit of the V0 sector of the vacuolar proton ATPase (ATP6V0C).Recent development of structural understandings reveals that ATP6V0C is not a simple pore-forming stalk enable to permeate transmitters.Therefore, it is time to review this topic revisited from the recent knowledge on ATPase.

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“…2,[14][15][16] Recently, it has also been shown that the V-ATPase a-subunit directly assembles with proteins that are not part of the V-ATPase complex including: (i) aldolase B, 17,18 (ii) phosphofrucktokinase-1, 19,20 (iii) calmodulin, 21 and (iv) t-SNARES syntaxin and SNAP-25. 22 However, the mechanisms and molecular details of interactions with these proteins remain poorly understood, mainly due to the lack of a high-resolution structure of the a-subunit and the absence of studies designed for mapping interaction sites on both the a-subunit and its associated proteins.…”

Section: Introductionmentioning

confidence: 99%

N‐terminal domain of the V‐ATPase a2‐subunit displays integral membrane protein properties

et al. 2010

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V-ATPase is a multisubunit membrane complex that functions as nanomotor coupling ATP hydrolysis with proton translocation across biological membranes. Recently, we uncovered details of the mechanism of interaction between the N-terminal tail of the V-ATPase a2-subunit isoform (a2N ) and ARNO, a GTP/GDP exchange factor for Arf-family small GTPases. Here, we describe the development of two methods for preparation of the a2N 1-402 recombinant protein in milligram quantities sufficient for further biochemical, biophysical, and structural studies. We found two alternative amphiphilic chemicals that were required for protein stability and solubility during purification: (i) non-detergent sulfobetaine NDSB-256 and (ii) zwitterionic detergent FOS-CHOLINEV R 12 (FC-12). Moreover, the other factors including mild alkaline pH, the presence of reducing agents and the absence of salt were beneficial for stabilization and solubilization of the protein. A preparation of a2N 1-402 in NDSB-256 was successfully used in pull-down and BIAcore TM protein-protein interaction experiments with ARNO, whereas the purity and quality of the second preparation in FC-12 was validated by size-exclusion chromatography and CD spectroscopy. Surprisingly, the detergent requirement for stabilization and solubilization of a2N 1-402 and its cosedimentation with liposomes were different from peripheral domains of other transmembrane proteins. Thus, our data suggest that in contrast to current models, so called ''cytosolic'' tail of the a2-subunit might actually be embedded into and/or closely associated with membrane phospholipids even in the absence of any obvious predicted transmembrane segments. We propose that a2N 1-402 should be categorized as an integral monotopic domain of the a2-subunit isoform of the V-ATPase.

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The v-ATPase V 0 Subunit a1 Is Required for a Late Step in Synaptic Vesicle Exocytosis in Drosophila

Cited by 284 publications

References 49 publications

The Protein Tyrosine Phosphatase SHP-1 Regulates Phagolysosome Biogenesis

The Protein Tyrosine Phosphatase SHP-1 Regulates Phagolysosome Biogenesis

Neurotransmitter release: vacuolar ATPase V0 sector c-subunits in possible gene or cell therapies for Parkinson’s, Alzheimer’s, and psychiatric diseases

N‐terminal domain of the V‐ATPase a2‐subunit displays integral membrane protein properties

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