Vacuolar ATPases and Their Role in Vision

Shine, Lisa; Kilty, Claire; Gross, Jeffrey M.; Kennedy, Breandán N.

doi:10.1007/978-1-4614-3209-8_13

Cited by 11 publications

(10 citation statements)

References 30 publications

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“…In osteoclasts of the bone, lysosomal V-ATPase translocates to the plasma membrane during bone resorption to acidify the lacunae [ 23 ]. Plasmalemmal V-ATPase is crucial to the functioning of interdental cells of the ear, epithelial cells of the nose and vision [ 24 – 26 ]. V-ATPase dysfunction is associated with pathological conditions like renal tubular acidosis, deafness, impairment of olfactory sense, and osteoporosis [ 27 – 29 ] A schematic outlining the role of V-ATPase in vesicular and luminal acidification is shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

“…The reduction in Notch signaling was due to mutated βA3/A1-crystallin, which regulates V-ATPase activity resulting in impaired endosomal acidification and γ-secretase activity thereby affecting the rate of Notch receptor processing [ 70 ]. This is an interesting finding considering that the role of V-ATPase in vision in now emerging [ 26 ]. Together these findings indicate that the regulation of Notch signaling by V-ATPase can have both positive and negative outcomes depending on the cellular localization of V-ATPase activity affected (endosomes vs lysosomes) and the dependence of Notch receptor processing on the endosomal pathway [ 71 , 72 ].…”

Section: Introductionmentioning

confidence: 99%

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The curious case of vacuolar ATPase: regulation of signaling pathways

et al. 2018

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The Vacuolar ATPase (V-ATPase) is a proton pump responsible for controlling the intracellular and extracellular pH of cells. The structure of V-ATPase has been highly conserved among all eukaryotic cells and is involved in diverse functions across species. V-ATPase is best known for its acidification of endosomes and lysosomes and is also important for luminal acidification of specialized cells. Several reports have suggested the involvement of V-ATPase in maintaining an alkaline intracellular and acidic extracellular pH thereby aiding in proliferation and metastasis of cancer cells respectively. Increased expression of V-ATPase and relocation to the plasma membrane aids in cancer modulates key tumorigenic cell processes like autophagy, Warburg effect, immunomoduation, drug resistance and most importantly cancer cell signaling. In this review, we discuss the direct role of V-ATPase in acidification and indirect regulation of signaling pathways, particularly Notch Signaling.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The curious case of vacuolar ATPase: regulation of signaling pathways

et al. 2018

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“…Mutations in ATP6V1B1 and ATP6V0A4 gene are the main cause responsible for recessive dRTA. To date, more than 30 ATP6V1B1 mutations and 40 ATP6V0A4 mutations have been described [1, 13, 14]. However, only few sporadic cases have been reported in China so far [15, 16].…”

Section: Discussionmentioning

confidence: 99%

Novel compound heterozygous ATP6V1B1 mutations in a Chinese child patient with primary distal renal tubular acidosis: a case report

Zhao

Gao

et al. 2018

BMC Nephrol

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BackgroundDistal renal tubular acidosis (dRTA) is a heterogeneous disorder characterized by normal anion gap metabolic acidosis. Autosomal recessive dRTA is usually caused by mutations occurring in ATP6V1B1 and ATP6V0A4 genes,encoding subunits B1 and a4 of apical H+-ATPase, respectively. The heterogeneous clinical manifestations of dRTA have been described in different ethnic groups harboring distinct mutations. Most of the reported cases are from Europe and Africa. At present, the prevalence of primary dRTA is still poorly elucidated in Chinese population.Case presentationA 2-year and six-month-old female patient was hospitalized because of recurrent hypokalemia, hyperchloremic metabolic acidosis and growth retardation. Laboratory investigations presented a normal anion gap hyperchloremic metabolic acidosis, hypokalemia, and inappropriate alkaline urine. Renal ultrasound indicated bilateral nephrocalcinosis. Bilateral sensorineural hearing loss (SNHL) was confirmed with moderately severe (45 dB) on the left ear and severe (80 dB) on the right ear, which was accompanied with enlarged vestibular aqueduct (EVA) on both sides. According to these findings, a diagnosis of dRTA was made. To identify the pathogenic gene mutation, all coding regions of ATP6V1B1 and ATP6V0A4 gene, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. The splicing variants were verified in peripheral blood leucocytes of the patient by RT-PCR. As a result, two novel heterozygous mutations in ATP6V1B1 were identified in the child. One mutation was a successive 2-nucleotide deletion in exon 2(c.133-134delTG), which caused a marked nonsense mediated mRNA decay. The other was a guanine to adenine substitution of the first nucleotide of intron 8(c.785 + 1 G > A), which led to the exclusion of exon 8. After treatment with sodium citrate, potassium citrateand citric acid, metabolic acidosis and hypokalemia were corrected, but her hearing decreased gradually during the 2 years and had to accept the use of bilateral hearing aids.ConclusionsWe described two novel dRTA associated mutations in ATP6V1B1 identified in a Chinese child patient accompanying with SNHL and EVA. Our study will help to expand the understanding of this rare disease in Chinese population.

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“…V-ATPase has an important vision supporting role in maintenance of central functions of RPE such as POS phagocytosis and autophagy where it has mainly been connected with its function in RPE lysosomes [38]. Additionally, it was found to have a role in RPE pigmentation in zebrafish [39].…”

Section: Discussionmentioning

confidence: 99%

Isolation of Intact and Functional Melanosomes from the Retinal Pigment Epithelium

et al. 2016

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Melanosomes of retinal pigment epithelium (RPE) have many vision supporting functions. Melanosome research would benefit from a method to isolate pure and characterized melanosomes. Sucrose gradient centrifugation is the most commonly used method for isolation of RPE melanosomes, but the isolated products are insufficiently characterized and their quality is unclear. Here we introduce a new gentle method for fractionation of porcine RPE that produces intact functional melanosomes with minimal cross-contamination from other cell organelles. The characterization of isolated organelles was conducted with several methods confirming the purity of the isolated melanosomal fraction (transmission electron microscopy, immunoblotting) and presence of the melanosomal membrane (fluorescence staining of melanosomal membrane, zeta potential measurement). We demonstrate that our isolation method produces RPE melanosomes with the ability to generate free phosphate (Pi) from ATP thereby proving that many membrane proteins remain functional after isolation. The isolated porcine RPE melanosomes represented V-type H+ATPase activity that was demonstrated with bafilomycin A1, a specific V-ATPase inhibitor. We anticipate that the isolation method described here can easily be optimized for the isolation of stage IV melanosomes from other pigmented cell types and tissues.

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Vacuolar ATPases and Their Role in Vision

Cited by 11 publications

References 30 publications

The curious case of vacuolar ATPase: regulation of signaling pathways

The curious case of vacuolar ATPase: regulation of signaling pathways

Novel compound heterozygous ATP6V1B1 mutations in a Chinese child patient with primary distal renal tubular acidosis: a case report

Isolation of Intact and Functional Melanosomes from the Retinal Pigment Epithelium

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