Dopamine release via the vacuolar ATPase V0 sector c-subunit, confirmed in N18 neuroblastoma cells, results in behavioral recovery in hemiparkinsonian mice

Jin, Duo; Muramatsu, Shin‐ichi; Shimizu, Nobuaki; Yokoyama, Shigeru; Hirai, Hirokazu; Yamada, Kiyofumi; Liu, Hongxiang; Higashida, Chiharu; Hashii, Minako; Higashida, Akihiko; Asano, Masahide; Ohkuma, Shoji; Higashida, Haruhiro

doi:10.1016/j.neuint.2011.12.021

Cited by 14 publications

(13 citation statements)

References 55 publications

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“…; Jin et al. ; Tomina and Takahata ). In addition, all three ciliates have the a‐subunit of the V O domain of V‐type ATPases.…”

Section: Resultsmentioning

confidence: 99%

“…Of the membrane-bound components of the F-or Vtype ATPases in ciliates, only c-subunits were detected in each organism. This could be because c-subunits can also function as ductin channels involved in the release of neurotransmitters (Bloc et al 2000;Jin et al 2012;Tomina and Takahata 2012). In addition, all three ciliates have the a-subunit of the V O domain of V-type ATPases.…”

Section: Superfamiliesmentioning

confidence: 99%

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Comparative Genomic Analysis of Integral Membrane Transport Proteins in Ciliates

Kumar

Saier

2014

J Eukaryotic Microbiology

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Integral membrane transport proteins homologous to those found in the Transporter Classification Database (TCDB; www.tcdb.org) were identified and bioinformatically characterized by transporter class, family, and substrate specificity in three ciliates, Paramecium tetraurelia (Para), Tetrahymena thermophila (Tetra), and Ichthyophthirius multifiliis (Ich). In these three organisms, 1,326 of 39,600 proteins (3.4%), 1,017 of 24,800 proteins (4.2%), and 504 out of 8,100 proteins (6.2%) integral membrane transport proteins were identified, respectively. Thus, an inverse relationship was observed between the % transporters identified and the number of total proteins per genome reported. This surprising observation provides insight into the evolutionary process, giving rise to genome reduction following whole genome duplication (as in the case of Para) or during pathogenic association with a host organism (Ich). Of these transport proteins in Para and Tetra, about 41% were channels (more than any other type of organism studied), 31% were secondary carriers (fewer than most eukaryotes) and 26% were primary active transporters, mostly ATP-hydrolysis driven (more than most other eukaryotes). In Ich, the number of channels was selectively reduced by 66%, relative to Para and Tetra. Para has four times more inorganic anion transporters than Tetra, and Ich has nonselectively lost most of these. Tetra and Ich preferentially transport sugars and monocarboxylates while Para prefers di-and tricarboxylates. These observations serve to characterize the transport proteins of these related ciliates, providing insight into their nutrition and metabolism.

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“…; Jin et al. ; Tomina and Takahata ). In addition, all three ciliates have the a‐subunit of the V O domain of V‐type ATPases.…”

Section: Resultsmentioning

confidence: 99%

Section: Superfamiliesmentioning

confidence: 99%

Comparative Genomic Analysis of Integral Membrane Transport Proteins in Ciliates

Kumar

Saier

2014

J Eukaryotic Microbiology

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“…Even if ATP6V0C expression patterns are found to be unaltered in human neurodegenerative disease, recent studies of ATP6V0C over-expression suggest the potential for its therapeutic benefit. Over-expression of ATP6V0C in mouse substantia nigra was shown recently to attenuate behavioral deficits following treatment with a dopaminergic neurotoxin [50], suggesting its potential utility as a therapeutic target for preventing neurodegeneration. Furthermore, over-expression of ATP6V0C has been shown in vitro to induce HIF-1α gene expression in a pH-independent manner [51] providing further proof of principle that over-expression of one subunit of V-ATPase has functional consequence.…”

Section: Discussionmentioning

confidence: 99%

ATP6V0C Knockdown in Neuroblastoma Cells Alters Autophagy-Lysosome Pathway Function and Metabolism of Proteins that Accumulate in Neurodegenerative Disease

et al. 2014

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ATP6V0C is the bafilomycin A1-binding subunit of vacuolar ATPase, an enzyme complex that critically regulates vesicular acidification. We and others have shown previously that bafilomycin A1 regulates cell viability, autophagic flux and metabolism of proteins that accumulate in neurodegenerative disease. To determine the importance of ATP6V0C for autophagy-lysosome pathway function, SH-SY5Y human neuroblastoma cells differentiated to a neuronal phenotype were nucleofected with non-target or ATP6V0C siRNA and following recovery were treated with either vehicle or bafilomycin A1 (0.3–100 nM) for 48 h. ATP6V0C knockdown was validated by quantitative RT-PCR and by a significant decrease in Lysostracker Red staining. ATP6V0C knockdown significantly increased basal levels of microtubule-associated protein light chain 3-II (LC3-II), α-synuclein high molecular weight species and APP C-terminal fragments, and inhibited autophagic flux. Enhanced LC3 and LAMP-1 co-localization following knockdown suggests that autophagic flux was inhibited in part due to lysosomal degradation and not by a block in vesicular fusion. Knockdown of ATP6V0C also sensitized cells to the accumulation of autophagy substrates and a reduction in neurite length following treatment with 1 nM bafilomycin A1, a concentration that did not produce such alterations in non-target control cells. Reduced neurite length and the percentage of propidium iodide-positive dead cells were also significantly greater following treatment with 3 nM bafilomycin A1. Together these results indicate a role for ATP6V0C in maintaining constitutive and stress-induced ALP function, in particular the metabolism of substrates that accumulate in age-related neurodegenerative disease and may contribute to disease pathogenesis.

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“…ATP6V0C plays a central role in H + transport as one part of the multi-subunit complex of ATPase [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. Israel and his group initially proposed that medatophore forms a proteinaceous pore by the six transmemebrane c subunits of ATPase [10,11].…”

Section: Mediatophore As An Ortholog Of Atpasementioning

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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Dopamine release via the vacuolar ATPase V0 sector c-subunit, confirmed in N18 neuroblastoma cells, results in behavioral recovery in hemiparkinsonian mice

Abstract: Abstract

Cited by 14 publications

References 55 publications

Comparative Genomic Analysis of Integral Membrane Transport Proteins in Ciliates

Comparative Genomic Analysis of Integral Membrane Transport Proteins in Ciliates

ATP6V0C Knockdown in Neuroblastoma Cells Alters Autophagy-Lysosome Pathway Function and Metabolism of Proteins that Accumulate in Neurodegenerative Disease

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

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