A5049372983- Ion Transport and Channel Regulation
- Pancreatic function and diabetes
- Amino Acid Enzymes and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Biomedical Research and Pathophysiology
- Autophagy in Disease and Therapy
- Neonatal Respiratory Health Research
- Calcium signaling and nucleotide metabolism
- Cancer, Hypoxia, and Metabolism
- Nitric Oxide and Endothelin Effects
- Epigenetics and DNA Methylation
- Heat shock proteins research
- interferon and immune responses
- Heme Oxygenase-1 and Carbon Monoxide
- Cellular transport and secretion
- Cystic Fibrosis Research Advances
- Chemokine receptors and signaling
- Membrane-based Ion Separation Techniques
- Mitochondrial Function and Pathology
- Hemoglobin structure and function
- Pregnancy and preeclampsia studies
- Electrolyte and hormonal disorders
- Congenital heart defects research
- Hormonal Regulation and Hypertension
Universitätsklinikum Gießen und Marburg
2023-2025
Université Paris Cité
2016-2024
Inserm
2016-2024
Sorbonne Université
2016-2024
Centre de Recherche des Cordeliers
2016-2024
Centre National de la Recherche Scientifique
2021-2024
Philipps University of Marburg
2020-2022
Centre National pour la Recherche Scientifique et Technique (CNRST)
2016
Three pregnancies with male offspring in one family were complicated by severe polyhydramnios and prematurity. One fetus died; the other two had transient massive salt-wasting polyuria reminiscent of antenatal Bartter’s syndrome.
Mutations in the renal specific Na-K-2Cl co-transporter (NKCC2) lead to type I Bartter syndrome, a life-threatening kidney disease featuring arterial hypotension along with electrolyte abnormalities. We have previously shown that NKCC2 and its disease-causing mutants are subject regulation by endoplasmic reticulum-associated degradation (ERAD). The aim of present study was identify protein partners specifically involved ERAD NKCC2. To this end, we screened cDNA library through yeast...
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,...
Mutations in MAGED2 cause transient antenatal Bartter syndrome (tBS) characterized by excessive amounts of amniotic fluid due to impaired renal salt transport via NKCC2 and NCC, high perinatal mortality, pre-term birth. Surprisingly, handling completely normalizes after Previously, we demonstrated that, under hypoxic conditions, depletion enhances endocytosis GalphaS (Gαs), reducing adenylate cyclase (AC) activation cAMP production. This signaling likely contributes the dysfunction...
Mutations in the Na-K-2Cl co-transporter NKCC2 lead to type I Bartter syndrome, a life-threatening kidney disease. We previously showed that export from ER constitutes limiting step maturation and cell surface expression. Yet, molecular mechanisms involved this process remain obscure. Here, we report identification of chaperone stress 70 protein (STCH) stress-inducible heat shock (Hsp70), as two novel binding partners ER-resident form NKCC2. STCH knock-down increased total expression whereas...
Mutations in MAGED2 cause transient Bartter syndrome characterized by severe renal salt wasting fetuses and infants, which leads to massive polyhydramnios causing preterm labor, extreme prematurity perinatal death. Notably, this condition resolves spontaneously parallel with developmental increase oxygenation. interacts G-alpha-S (Gαs). Given the role of Gαs activating adenylyl cyclase at plasma membrane consequently generating cAMP promote reabsorption via protein kinase A (PKA), we...
Hypoxia stabilizes the transcription factor HIF-1α, which promotes of many genes essential to adapt reduced oxygen levels. Besides proline hydroxylation, expression HIF-1α is also regulated by a range other posttranslational modifications including phosphorylation cAMP-dependent protein kinase A (PKA), HIF-1α. We recently demonstrated that MAGED2 required for cAMP generation under hypoxia and proposed this regulation may explain transient nature antenatal Bartter syndrome (aBS) due...
Melanoma-associated antigen D2 (MAGED2) plays an essential role in activating the cAMP/PKA pathway under hypoxic conditions, which is crucial for stimulating renal salt reabsorption and thus explaining transient variant of Bartter's syndrome. The also known to regulate autophagy, a lysosomal degradation process induced by cellular stress. Previous studies showed that two members melanoma-associated antigens MAGE-family inhibit autophagy. To explore potential MAGED2 stress-induced specific...
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...