A5060829616- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Biomedical Research and Pathophysiology
- Pancreatic function and diabetes
- Cardiac electrophysiology and arrhythmias
- CRISPR and Genetic Engineering
- Digestive system and related health
- Neuroscience and Neuropharmacology Research
- Erythrocyte Function and Pathophysiology
- Amino Acid Enzymes and Metabolism
- Molecular Biology Techniques and Applications
- Diabetes Treatment and Management
- Sleep and Wakefulness Research
- RNA Research and Splicing
- Protein Tyrosine Phosphatases
- Wnt/β-catenin signaling in development and cancer
- Animal Genetics and Reproduction
- Cystic Fibrosis Research Advances
- Metabolism and Genetic Disorders
- Cancer, Hypoxia, and Metabolism
- Cellular transport and secretion
- Pluripotent Stem Cells Research
- Plant-based Medicinal Research
- Olfactory and Sensory Function Studies
- RNA regulation and disease
Inserm
2018-2024
Université Paris Cité
2018-2024
Sorbonne Université
2017-2024
Centre National de la Recherche Scientifique
2018-2024
Centre de Recherche des Cordeliers
2017-2024
Université Sorbonne Nouvelle
2023
Metabolism and Renal Physiology
2016-2022
Délégation Paris 5
2018-2019
Sorbonne Paris Cité
2019
Inactivating mutations of kidney Na-K-2Cl cotransporter NKCC2 lead to antenatal Bartter syndrome (BS) type 1, a life-threatening salt-losing tubulopathy. We previously reported that this serious inherited renal disease is linked the endoplasmic reticulum-associated degradation (ERAD) pathway. The purpose work characterize further ERAD machinery NKCC2. Here, we report identification ancient ubiquitous protein 1 (AUP1) as novel interactor ER-resident form in cells. AUP1 also an ER lectin OS9,...
Dent disease is an X-linked recessive renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive failure. Inactivating mutations of CLCN5, the gene encoding 2Cl−/H+ exchanger ClC-5, have been reported in patients with 1. In vivo studies mice harboring artificial mutation "gating glutamate" ClC-5 (c.632A > C, p.Glu211Ala) mathematical modeling suggest that endosomal chloride concentration could be important...
This study highlights new regulatory and conductive properties of the as yet poorly molecularly defined 70-pS K + channel in apical membrane thick ascending limb Henle’s loop cells mouse kidney that functionally identify it a large-conductance, Na - Cl – -activated 1.1-like channel.
Mutations in Na-K-2Cl co-transporter, NKCC2, lead to type I Bartter syndrome (BS1), a life-threatening kidney disease. Yet, our knowledge of the molecular regulation NKCC2 mutants remains poor. Here, we aimed identify pathogenic mechanisms one novel and three previously reported missense mutations. Co-immunolocalization studies revealed that all variants are not functional because they expressed at cell surface due retention endoplasmic reticulum (ER). Cycloheximide chase assays together...
Mutations in the apically located kidney Na-K-2Cl cotransporter NKCC2 cause type I Bartter syndrome, a life-threatening disorder. We previously showed that transport from ER represents limiting phase journey to cell surface. Yet very little is known about quality control components specific and its disease-causing mutants. Here, we report identification of Golgi alpha1, 2-mannosidase IA (ManIA) as novel binding partner immature form NKCC2. ManIA interaction with takes place mainly at...
Mutations in the apical Na-K-2Cl co-transporter, NKCC2, cause type I Bartter syndrome (BS1), a life-threatening kidney disease. We have previously demonstrated that BS1 variant Y998X, which deprives NKCC2 from its highly conserved dileucine-like motifs, compromises co-transporter surface delivery through ER retention mechanisms. However, whether these hydrophobic motifs are sufficient for anterograde trafficking of remains to be determined. Interestingly, sequence analysis C-terminus...
Pathological missense mutations in CLCNKB gene give a wide spectrum of clinical phenotypes Bartter syndrome type III patients. Molecular analysis the mutated ClC-Kb channels can be helpful to classify according their functional alteration. We investigated consequences nine causing syndrome. first established that all tested lead decreased currents. Combining electrophysiological and biochemical methods Xenopus laevis oocytes MDCKII cells, we identified three classes mutations. One class is...
Mutations in the CLCN5 gene encoding 2Cl- /1H+ exchanger ClC-5 are associated with Dent disease 1, an inherited renal disorder characterized by low-molecular-weight (LMW) proteinuria and hypercalciuria. In kidney, is mostly localized proximal tubule cells, where it thought to play a key role endocytosis of LMW proteins. Here, we investigated consequences eight previously reported pathogenic missense mutations surrounding "proton glutamate" that serves as crucial H+ -binding site for...
Dent's disease is an X‐linked recessive renal tubular disorder characterized by low‐molecular‐weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive failure, inconstantly associated with other proximal dysfunctions. Inactivating mutations of CLCN5 , the gene encoding 2Cl − /H + exchanger ClC‐5, are type 1. In kidney, ClC‐5 predominantly expressed at apical membrane tubule cells on early endosomes. Impaired endosomal acidification consecutive to...
Dent Disease is a rare X‐linked inherited renal proximal disorder characterized by low molecular weight (LMW) proteinuria, hypercalciuria, kidney stones and progressive failure. Inactivating mutations of the CLCN5 gene encoding 2Cl − /H + exchanger ClC‐5 have been identified in approximately two‐thirds patients with Disease. predominantly expressed early endosomes tubules where it optimizes function vacuolar H pump to ensure an efficient endocytosis LMW proteins. We previously investigated...
Mutations in the CLCN5 gene encoding 2Cl-/1H+ exchanger ClC-5 are associated with Dent disease 1, an inherited renal disorder characterized by low molecular weight (LMW) proteinuria and hypercalciuria. In kidney, is mostly localized proximal tubule cells where it thought to play a key role endocytosis of LMW proteins. Here, we investigated consequences eight previously reported pathogenic missense mutations surrounding “proton glutamate” that serves as crucial H+-binding site for exchanger....
Dent's disease is a rare renal tubular disorder characterized by low-molecular-weight-proteinuria, hypercalciuria with nephrocalcinosis or nephrolithiasis, and progressive failure. It frequently associated inactivating mutations of the CLCN5gene coding for 2Cl- /H+ exchanger ClC-5. In kidney, ClC-5 mainly expressed in early endosomes proximal tubules (PT) cells where it optimizes function vacuolar H+ -ATPase to ensure proper endocytosis low-molecular-weight-proteins. To better understand...