(Pro)renin receptor and V-ATPase: from <i>Drosophila</i> to humans

Rousselle, Anthony; Sihn, Gabin; Rotteveel, Martijn; Bäder, Michael

doi:10.1042/cs20130307

Cited by 17 publications

(16 citation statements)

References 66 publications

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“…This has an overall impact on tumor growth and metastasis via the modulated signals and their pathways. Crucial tumor associated pathways such as Notch, wnt, mTOR [ 49 – 50 ] are modulated by V-ATPase through endosomal trafficking and pH maintenance. The colocalization of V0a2 isoforms with endosomes suggests that it may be a component of endosomal V-ATPase machinery and can be targeted for modulating the tumor associated signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Vacuolar ATPase ‘a2’ isoform exhibits distinct cell surface accumulation and modulates matrix metalloproteinase activity in ovarian cancer

et al. 2015

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Tumor associated vacuolar H+-ATPases (V-ATPases) are multi-subunit proton pumps that acidify tumor microenvironment, thereby promoting tumor invasion. Subunit ‘a’ of its V0 domain is the major pH sensing unit that additionally controls sub-cellular targeting of V-ATPase and exists in four different isoforms. Our study reports an elevated expression of the V-ATPase-V0a2 isoform in ovarian cancer(OVCA) tissues and cell lines(A2780, SKOV-3 and TOV-112D). Among all V0’a’ isoforms, V0a2 exhibited abundant expression on OVCA cell surface while normal ovarian epithelia did not. Sub-cellular distribution of V-ATPase-V0a2 confirmed its localization on plasma-membrane, where it was also co-associated with cortactin, an F-actin stabilizing protein at leading edges of cancer cells. Additionally, V0a2 was also localized in early and late endosomal compartments that are sites for modulations of several signaling pathways in cancer. Targeted inhibition of V-ATPase-V0a2 suppressed matrix metalloproteinase activity(MMP-9 & MMP-2) in OVCA cells. In conclusion, V-ATPase-V0a2 isoform is abundantly expressed on ovarian tumor cell surface in association with invasion assembly related proteins and plays critical role in tumor invasion by modulating the activity of matrix-degrading proteases. This study highlights for the first time, the importance of V-ATPase-V0a2 isoform as a distinct biomarker and possible therapeutic target for treatment of ovarian carcinoma.

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Section: Discussionmentioning

confidence: 99%

Vacuolar ATPase ‘a2’ isoform exhibits distinct cell surface accumulation and modulates matrix metalloproteinase activity in ovarian cancer

et al. 2015

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“…Besides the physiological function of PRR in the kidney, PRR is well known to regulate development and integrity of multiple tissue types, as highlighted by pathological abnormalities and lethality induced by systemic or organ-specific deletion of PRR (38)(39)(40). In particular, RT PRR-KO mice develop prominent autophagosome accumulation in the TAL and, to a lesser extent, in the CD, which has been postulated to contribute to decreased expression of NKCC2, as well as AQP2 (12).…”

Section: Figure 7 Analysis Of Renal Expression Of V 2 R and Transpormentioning

confidence: 99%

Site-1 protease–derived soluble (pro)renin receptor targets vasopressin receptor 2 to enhance urine concentrating capability

Wang¹,

Xu²,

Luo³

et al. 2019

JCI Insight

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“…It is evident that PRR acts in a renin-independent manner in low vertebrates (1,37,(39)(40)(41)). PRR appears to be similarly involved in the regulation of embryogenesis in mammals, as evidenced by the lethal phenotype in mice with systemic or tissue-specific deletion of PRR (1,4).…”

Section: Induction Of Diabetes Insipidus and Suppression Of Renal Prrmentioning

confidence: 99%

Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor

Wang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

135

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The extracellular domain of the (pro)renin receptor (PRR) is cleaved to produce a soluble (pro)renin receptor (sPRR) that is detected in biological fluid and elevated under certain pathological conditions. The present study was performed to define the antidiuretic action of sPRR and its potential interaction with liver X receptors (LXRs), which are known regulators of urine-concentrating capability. Water deprivation consistently elevated urinary sPRR excretion in mice and humans. A template-based algorithm for protein-protein interaction predicted the interaction between sPRR and frizzled-8 (FZD8), which subsequently was confirmed by coimmunoprecipitation. A recombinant histidine-tagged sPRR (sPRR-His) in the nanomolar range induced a remarkable increase in the abundance of renal aquaporin 2 (AQP2) protein in primary rat inner medullary collecting duct cells. The AQP2 up-regulation relied on sequential activation of FZD8-dependent β-catenin signaling and cAMP-PKA pathways. Inhibition of FZD8 or tankyrase in rats induced polyuria, polydipsia, and hyperosmotic urine. Administration of sPRR-His alleviated the symptoms of diabetes insipidus induced in mice by vasopressin 2 receptor antagonism. Administration of the LXR agonist TO901317 to C57/BL6 mice induced polyuria and suppressed renal AQP2 expression associated with reduced renal PRR expression and urinary sPRR excretion. Administration of sPRR-His reversed most of the effects of TO901317. In cultured collecting duct cells, TO901317 suppressed PRR protein expression, sPRR release, and PRR transcriptional activity. Overall we demonstrate, for the first time to our knowledge, that sPRR exerts antidiuretic action via FZD8-dependent stimulation of AQP2 expression and that inhibition of this pathway contributes to the pathogenesis of diabetes insipidus induced by LXR agonism.soluble (pro)renin receptor | liver X receptor | aquaporin-2 | frizzled-8 | β-catenin F ull-length (Pro)renin receptor (PRR), a 350-amino acid transmembrane receptor for prorenin and renin, is subjected to protease-mediated cleavage to produce a 28-kDa protein of the N-terminal extracellular domain, the soluble (pro)renin receptor (sPRR), and the 8.9-kDa C-terminal intracellular domain called "M8.9" (1, 2). Before the cloning of full-length PRR in mesangial cells as an integral 39-kDa membrane protein (3), M8.9 was identified as a truncated protein associated with the vacuolar H + -ATPase (V-ATPase) from bovine chromatin granules (4). The cleavage occurs in Golgi apparatus through furin (5) or ADMA19 (6). An sPRR ELISA kit has been developed to detect sPRR in plasma and urine samples (7) . With this assay, increased serum sPRR levels have been demonstrated in patients with heart failure (8), kidney disease (9, 10), hypertension (11), and preeclampsia (2). Moreover, serum sPRR is positively associated with serum creatinine, blood urea nitrogen, and urine protein and is inversely associated with the estimated glomerular filtration rate in patients with chronic kidney disease caused by hypertension...

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(Pro)renin receptor and V-ATPase: from Drosophila to humans

Cited by 17 publications

References 66 publications

Vacuolar ATPase ‘a2’ isoform exhibits distinct cell surface accumulation and modulates matrix metalloproteinase activity in ovarian cancer

Vacuolar ATPase ‘a2’ isoform exhibits distinct cell surface accumulation and modulates matrix metalloproteinase activity in ovarian cancer

Site-1 protease–derived soluble (pro)renin receptor targets vasopressin receptor 2 to enhance urine concentrating capability

Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor

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