A5001810791- Cellular transport and secretion
- Amino Acid Enzymes and Metabolism
- Biomedical Research and Pathophysiology
- Calcium signaling and nucleotide metabolism
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Neonatal Health and Biochemistry
- Ion channel regulation and function
- Erythrocyte Function and Pathophysiology
- Receptor Mechanisms and Signaling
- Glycosylation and Glycoproteins Research
- Porphyrin Metabolism and Disorders
- Folate and B Vitamins Research
- Carbohydrate Chemistry and Synthesis
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- Metabolism and Genetic Disorders
- Polyamine Metabolism and Applications
- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Lipid Membrane Structure and Behavior
- Pharmacogenetics and Drug Metabolism
- Adenosine and Purinergic Signaling
- GABA and Rice Research
- Cancer, Hypoxia, and Metabolism
Université Paris Cité
2015-2025
SPPIN - Saints-Pères Paris Institute for Neurosciences
2019-2025
Institut de Psychiatrie et Neurosciences de Paris
2019-2025
Centre National pour la Recherche Scientifique et Technique (CNRST)
2023
Centre National de la Recherche Scientifique
2010-2021
Sorbonne Paris Cité
2012-2018
Neurophotonics Laboratory
2016-2018
Délégation Paris 5
2011-2017
Institut de Biologie Physico-Chimique
1991-2010
Sorbonne Université
1987-2008
The unc‐47 locus of Caenorhabditis elegans has been suggested to encode a synaptic vesicle GABA transporter. Here we used hydropathy plot analysis identify candidate vesicular transporter in genomic sequences derived from region the physical map comprising . A mouse homologue was identified and cloned EST database information. In situ hybridization rat brain revealed codistribution with both GABAergic glycinergic neuronal markers. Moreover, expression COS‐7 PC12 cells induced an...
In eukaryotic cells, lysosomes represent a major site for macromolecule degradation. Hydrolysis products are eventually exported from this acidic organelle into the cytosol through specific transporters. Impairment of process at either hydrolysis or efflux step is responsible several lysosomal storage diseases. However, most transporters, although biochemically characterized, remain unknown molecular level. study, we report and functional characterization amino acid transporter (LYAAT-1),...
Lysosomes are membrane-bound endocytic organelles that play a major role in degrading cell macromolecules and recycling their building blocks. A comprehensive knowledge of the lysosome function requires an extensive description its content, issue partially addressed by previous proteomic analyses. However, proteins underlying many lysosomal membrane functions, including numerous transporters, remain unidentified. We performed comparative, semi-quantitative analysis rat liver...
Cystinosin, the lysosomal cystine exporter defective in cystinosis, is founding member of a family heptahelical membrane proteins related to bacteriorhodopsin and characterized by duplicated motif termed PQ loop. PQ-loop are more frequent eukaryotes than prokaryotes; except for cystinosin, their molecular function remains elusive. In this study, we report that three yeast unknown function, Ypq1, Ypq2, Ypq3, localize vacuolar involved homeostasis cationic amino acids (CAAs). We also show...
Glial cells are increasingly recognized as active players that profoundly influence neuronal synaptic transmission by specialized signaling pathways. In particular, astrocytes have been shown recently to release small molecules, such the amino acids l -glutamate and d -serine “gliotransmitters,” which directly control efficacy of adjacent synapses. However, it is still controversial whether gliotransmitters released from a cytosolic pool or Ca 2+ -dependent exocytosis secretory vesicles,...
Significance Lysosomes are degradative intracellular organelles essential to cell maintenance and homeostasis. Although their function is well documented, the proteins responsible for efflux, reuse, of lysosomal degradation products remain largely unknown. In this study, we identify transporter efflux glutamine, an amino acid central several key metabolic pathways. This role glutamine exploited by types cancer cells with increased consumption glutamine. Interestingly, genetic inactivation...
Abstract The lysosomal degradation of macromolecules produces diverse small metabolites exported by specific transporters for reuse in biosynthetic pathways. Here we deorphanized the major facilitator superfamily domain containing 1 (MFSD1) protein, which forms a tight complex with glycosylated membrane protein (GLMP) membrane. Untargeted metabolomics analysis MFSD1-deficient mouse lysosomes revealed an increase cationic dipeptides. Purified MFSD1 selectively bound dipeptides, while...
meta-Iodobenzylguanidine, an adrenal imaging agent used for the scintigraphic detection of human pheochromocytoma, is a substrate monoamine uptake system chromaffin granules. It accumulated by bovine granule membrane vesicles in presence ATP, and it can be released osmotic shock. The dependent upon generation H+-electrochemical gradient ATP-dependent H+ pump since blocked ionophore meta-iodobenzylguanidine driven imposing artificial pH (inside acidic) on vesicles. transport saturable its Km...
The vesicular monoamine transporter, which catalyses a H+/monoamine antiport in monoaminergic vesicle membrane, is very hydrophobic intrinsic membrane protein. After solubilization, this protein was found to have high tendency aggregate, as shown by SDS/PAGE, especially when samples were boiled the classical Laemmli buffer before electrophoresis. This behaviour analysed some detail. aggregation promoted temperatures, organic solvents and acidic pH, suggesting that it resulted from unfolding...
In monoaminergic cells, the neurotransmitter is accumulated into secretory or synaptic vesicles by a tetrabenazine‐ and reserpine‐sensitive transporter, catalyzing an H + /monoamine antiport. The major vesicular monoamine transporter from bovine chromaffin cells was cloned, using sequences common to adrenal medulla brain rat transporters. Its identity confirmed peptide sequences, determined purified protein. Surprisingly, sequence, bVMAT 2 , more related human than that medulla. PCR...
Neuronal ceroid lipofuscinoses (NCLs) constitute a group of progressive neurodegenerative disorders resulting from mutations in at least eight different genes. Mutations the most recently identified NCL gene, MFSD8/CLN7 , underlie variant late-infantile (vLINCL). The gene encodes polytopic protein with unknown function, which shares homology ion-coupled membrane transporters. In this study, we confirmed lysosomal localization native CLN7 protein. This is not impaired by presence pathogenic...
Secondary active transporters use electrochemical gradients provided by primary ion pumps to translocate metabolites or drugs “uphill” across membranes. Here we report the ion-coupling mechanism of cystinosin, an unusual eukaryotic, proton-driven transporter distantly related proton pump bacteriorhodopsin. In humans, cystinosin exports proteolysis-derived dimeric amino acid cystine from lysosomes and is impaired in cystinosis. Using voltage-dependence analysis steady-state transient currents...
DIRC2 (Disrupted in renal carcinoma 2) has been initially identified as a breakpoint-spanning gene chromosomal translocation putatively associated with the development of cancer. The protein belongs to MFS (major facilitator superfamily) and previously detected by organellar proteomics tentative constituent lysosomal membranes. In present study, residence overexpressed well endogenous was shown several approaches. is proteolytically processed into N-glycosylated N-terminal non-glycosylated...
Congenital disorders of glycosylation are severe inherited diseases in which aberrant protein is a hallmark. Transmembrane 165 (TMEM165) novel Golgi transmembrane involved type II congenital glycosylation. Although its biologic function still controversial issue, we have demonstrated that the defect due to TMEM165 deficiency resulted from Mn2+ homeostasis defect. The goal this study was delineate cellular pathway by extracellular rescues N-glycosylation knockout (KO) cells. We first after...