The B1 H+-ATPase (Atp6v1b1) Subunit in Non–Type A Intercalated Cells is Required for Driving Pendrin Activity and the Renal Defense Against Alkalosis DOI
Soline Bourgeois,

Jana Kovacikova,

Milica Bugarski

et al.

Journal of the American Society of Nephrology, Journal Year: 2023, Volume and Issue: 35(1), P. 7 - 21

Published: Nov. 22, 2023

Significance Statement In the kidney, B1 H + -ATPase subunit is mostly expressed in intercalated cells (IC). Its importance acid-secreting type A ICs evident patients with inborn distal renal tubular acidosis and ATP6V1B1 mutations. However, protein also highly alkali-secreting non–type where its function incompletely understood. We demonstrate Atp6v1b1 knock out mice that critical for response to defend against alkalosis during an alkali load or chronic furosemide treatment. These findings highlight of maintaining acid–base balance metabolic challenges commonly used diuretics. Background Non–type collecting duct system express luminal Cl − /HCO 3 exchanger pendrin apical and/or basolateral -ATPases containing isoform. excrete bicarbonate alkalosis. Mutations (ATP6V1B1) cause due role acid secretory ICs. The has remained elusive. Methods examined responses −/− +/+ treatment furosemide. Results An 1 week resulted a more pronounced hypokalemic male ATP6v1b1 versus could not be compensated by respiration. Total expression activity ex vivo microperfused cortical ducts were reduced, β 2 -adrenergic stimulation was blunted mice. Basolateral strongly although B2 isoform increased. Ligation assays subunits indicated impaired assembly V 0 domains. During treatment, showed polyuria hyperchloremia . pendrin, water channel AQP2, epithelial sodium ENaC reduced. Conclusions Our data protecting reveal hitherto unrecognized need proper complexes ability stimulated.

Language: Английский

Structural and functional understanding of disease-associated mutations in V-ATPase subunit a1 and other isoforms DOI Creative Commons
Karen Indrawinata, Peter Argiropoulos, Shuzo Sugita

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: July 3, 2023

The vacuolar-type ATPase (V-ATPase) is a multisubunit protein composed of the cytosolic adenosine triphosphate (ATP) hydrolysis catalyzing V1 complex, and integral membrane Vo, responsible for proton translocation. largest subunit Vo a, enables translocation upon ATP hydrolysis, mediated by complex. Four known isoforms (a1-a4) are expressed in different cellular locations. Subunit a1 (also as Voa1), neural isoform, strongly neurons encoded ATP6V0A1 gene. Global knockout this gene mice causes embryonic lethality, whereas pyramidal neuron-specific resulted neuronal cell death with impaired spatial learning memory. Recently reported, de novo biallelic mutations human impair autophagic lysosomal activities, contributing to developmental epileptic encephalopathies (DEE) early onset progressive myoclonus epilepsy (PME). heterozygous R740Q mutation most recurrent variant reported cases DEE. Homology studies suggest R740 deprotonates protons from specific glutamic acid residues c, highlighting its importance overall V-ATPase function. In paper, we discuss structure mechanism V-ATPase, emphasizing how can lead dysfunction neurodevelopmental disorders, non-neural isoforms, a2-a4, also various genetic diseases. Given growing discovery disease-causing variants function pump-based regulator intracellular organelle pH, multiprotein complex warrants further investigation.

Language: Английский

Citations

9
Nephrocalcinosis in Neonates DOI

Gia J. Oh,

Lavjay Butani

NeoReviews, Journal Year: 2024, Volume and Issue: 25(2), P. e88 - e98

Published: Feb. 1, 2024

Nephrocalcinosis occurs in as many 40% of preterm neonates. Many causes and contributors predispose neonates to develop nephrocalcinosis, including metabolic, genetic, iatrogenic factors. Because nephrocalcinosis can be a manifestation an underlying genetic disorder, with must undergo evaluation identify address contributors, prevent further renal calcium deposition that potentially lead dysfunction. In this article, we review the epidemiology, pathogenesis, diagnosis, We also summarize natural history prematurity well management condition.

Language: Английский

Citations

3
Renal Tubular Defects DOI

Chang Huei Chen,

Michel Chonchol

Oxford University Press eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 303 - 304

Published: April 1, 2025

Abstract This chapter guides the reader on diagnosis and management of renal tubular defects in hospitalized patients.

Language: Английский

Citations

0
Hydration for Adult Patients with Nephrolithiasis: Specificities and Current Recommendations DOI Open Access
Marie Courbebaisse, Simon Travers, Élise Bouderlique

et al.

Nutrients, Journal Year: 2023, Volume and Issue: 15(23), P. 4885 - 4885

Published: Nov. 22, 2023

Nephrolithiasis affects around 10% of the population and is frequently associated with impaired dietary factors. The first one insufficient fluid intake inducing reduced urine volume, supersaturation, subsequently urinary lithiasis. Kidneys regulate 24 h which, under physiological conditions, approximately reflects daily intake. aim this study to synthesize highlight role hydration in treatment nephrolithiasis. Increasing has a preventive effect on risk developing kidney stone (primary prevention) also decreases recurrence (secondary prevention). Current guidelines recommend increasing at least 2.5 L/day prevent formation, even 3.5-4 L some severe forms nephrolithiasis or enteric hyperoxaluria cystinuria). Fluid must be balanced between day night, avoid supersaturation during night. Patients should informed supported difficult process dilution, practical ways routines increase their liquid choice water, which chosen depending its composition (such as calcium, bicarbonate, magnesium content). Finally, additional advice given certain beverages such those containing fructose phosphoric acid, are susceptible

Language: Английский

Citations

6
Novel functions of the anion exchanger AE4 (SLC4A9) DOI Creative Commons

Helga Vitzthum,

Catherine Meyer-Schwesinger, Heimo Ehmke

et al.

Pflügers Archiv - European Journal of Physiology, Journal Year: 2024, Volume and Issue: 476(4), P. 555 - 564

Published: Jan. 9, 2024

Abstract The kidney plays a crucial role in acid-base homeostasis. In the distal nephron, α-intercalated cells contribute to urinary acid (H + ) secretion and β-intercalated accomplish base (HCO 3 - secretion. regulate status through modulation of apical Cl /HCO exchanger pendrin (SLC26A4) activity. this review, we summarize discuss our current knowledge physiological renal transporter AE4 (SLC4A9). AE4, as cation-dependent exchanger, is exclusively expressed basolateral membrane essential for sensing metabolic disturbances mice, but not sodium reabsorption plasma volume control. Potential intracellular signaling pathways are discussed that might link

Language: Английский

Citations

2
Intercalated cell function, kidney innate immunity, and urinary tract infections DOI
Andrew L. Schwaderer, Evan Rajadhyaksha, Jorge Canas

et al.

Pflügers Archiv - European Journal of Physiology, Journal Year: 2024, Volume and Issue: 476(4), P. 565 - 578

Published: Jan. 16, 2024

Language: Английский

Citations

2
Alteration of bone microarchitecture in hereditary distal RTA patients with SLC4A1 gene mutation: assessed by HR-pQCT DOI Creative Commons
Rong Chen, Lijia Cui, Juan Du

et al.

The Journal of Clinical Endocrinology & Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 16, 2024

Abstract Context Hereditary distal renal tubular acidosis caused by SLC4A1 gene mutation (SLC4A1-dRTA) is a rare hereditary form of acidosis. Rickets or osteomalacia common complication SLC4A1-dRTA and seriously affects patients’ daily lives. However, studies on the bone microstructure in are limited. Objective This work aimed to evaluate patients, compared age- sex-matched healthy controls X-linked hypophosphatemic rickets (XLH) patients. Methods was retrospective study 11 Clinical manifestations biochemical radiographical examinations were characterized. Bone examined 7 controls, 21 XLH patients using high-resolution peripheral quantitative computed tomography. Results Skeletal symptoms, including fracture, pain, lower limb deformity, present 72.7% Short stature 63.6% had significantly volumetric mineral density tibia more severe deteriorated trabecular radius than controls. severely With long-term alkaline therapy, alleviated pain increased height. Conclusion lesions clinical Compared with XLH, another type rickets, damage, further supporting necessity early diagnosis timely treatment disease.

Language: Английский

Citations

2
A ONECUT1 regulatory, non-coding region in pancreatic development and diabetes DOI Creative Commons
Sarah K. Merz, Valérie Senée, Anne Philippi

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(11), P. 114853 - 114853

Published: Oct. 19, 2024

Citations

2
Unraveling the molecular landscape of kAE1: a narrative review DOI
Priyanka Mungara,

Moubarak Waiss,

Sunny Hartwig

et al.

Canadian Journal of Physiology and Pharmacology, Journal Year: 2024, Volume and Issue: 102(7), P. 396 - 407

Published: April 26, 2024

Kidney anion exchanger 1 (kAE1) is an isoform of the AE1 protein encoded by SLC4A1 gene. It a basolateral membrane expressed α-intercalated cells in connecting tubules and collecting duct kidney. Its main function to exchange bicarbonate chloride ions between blood urine maintain pH at physiological threshold. The kAE1 undergoes multiple post-translational modifications such as phosphorylation ubiquitination interacts with many different proteins claudin-4 carbonic anhydrase II. Mutations gene may lead development distal renal tubular acidosis, characterized failure acidify urine, which result nephrocalcinosis more severe cases, failure. In this review, we discuss structure kAE1, its modifications, protein–protein interactions. Finally, insights gained from study mutations humans mice.

Language: Английский

Citations

1
Insights from a Brief Study of Renal Calculi: Recent Diagnostic and Treatment Approaches DOI Creative Commons
Aashish Kumar, Rajat Goyal,

Kajal Garg

et al.

Journal of Bio-X Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Background: Renal calculi, commonly known as kidney stones, is a prevalent urological condition that affects substantial portion of the population worldwide. The formation stones complex process influenced by various factors, including diet, fluid intake, genetics, and metabolic abnormalities. pathogenesis renal calculi involves interplay multiple supersaturation urine with stone-forming constituents, urinary supersaturation, crystallization, aggregation. Objective: This review aims to provide an overview present understanding their pathophysiology, diagnostic approaches, available treatment modalities. Methods: discusses different types such calcium oxalate, phosphate, uric acid, struvite explores mechanisms associated risk factors. management relies on stone characteristics, patient symptoms, size, location. Furthermore, counseling education regarding lifestyle modifications factor are essential for long-term management. Conclusion: Accurate diagnosis appropriate based characteristics symptoms successful outcomes. Preventive strategies reduce recurrence vital well-being. However, further research needed refine techniques, improve options, enhance underlying pathophysiology calculi.

Language: Английский

Citations

1