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A. , at 1/1000), rabbit anti-GON7 (HPA 051832, used at 1:500), rabbit anti-LAGE3 (HPA 036122, used at 1/500), rabbit anti-TPRKB (HPA035712, used at 1:500), rabbit anti-OSGEP (HPA 039751, used at 1/1000), and mouse anti-GAPDH (MAB374, used at 1/2000) from Sigma-Aldrich; mouse anti-V5 (MCA1360, used at 1/1000) from Bio-Rad; rabbit anti-YRDC (PA5-56366, used at 1:500) from ThermoFisher Scientific; rabbit anti-LAGE3 (NBP2-32715, used at 1:1000) and mouse anti-OSGEP (NBP2-00823, used at 1:500) from Novus Biologicals; rabbit anti-TP53RK (AP17010b, used at 1:500) from Abgent. Secondary antibodies for immunoblotting were sheep: anti-mouse and donkey anti-rabbit HRP-conjugated antibodies (GE Healthcare, UK), and IRDye 800CW Donkey anti-rabbit (926-32213) and IRDye 680RD Donkey antimouse (926-68072) antibodies (LI-COR), The following antibodies were used in the study: mouse anti-?-tubulin (T5168, used at 1:1000), mouse anti-actin (A5316, used at 1:1000), mouse anti-HA (12CA5

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R. S. Author, O. G. , O. B. , E. M. , F. N. et al., Antignac recruited patients and collected detailed clinical information for the study. N.B. provided MRI from control individuals and critically interpreted MRI images from patients, and A.M.v.E. provided and analyzed images of renal histology and electron microscopy

J. P. Arrondel, B. C. , D. L. , G. Martin, E. M. et al., performed cell experiments (co-immunoprecipitation, cycloheximide chase, cell culture), qPCR, and western blot experiments. S.M. performed proteins expression and purifications, cristallogenesis trials, diffraction data collection, 3D structure resolution, SAXS data collection, and analysis. B.C. performed OSGEP/ LAGE3/GON7-his expression and purification, and nucleosides preparation from tRNA samples and YRDC WT and mutant enzymatic assay. D.L. performed yeast complementation studies, expression, and purification of yeast tRNAs. D.D. performed SAXS data collection and analysis. E.L. collected and analyzed NMR experiments. A.-C.B. and S.S. performed HPLC MS/MS t 6 A modification analysis. G. Mollet, G. Martin, and I.C.G. performed proteomic studies in human podocyte cell lines. P.R. performed telomere restriction-fragment assays

G. Mollet, H. V. , C. C. , D. L. , S. M. et al., Antignac conceived and coordinated the study, and wrote the manuscript with the input of

, Laurine Buscara 1 , Gaëlle Martin 1 , Eduardo Machuca 1 , Fabien Nevo 1, Sophie Collardeau-Frachon, vol.6

C. Cnrs and U. Paris-sud, 13 Inserm UMR1163, Laboratory of Genome Dynamics in the Immune System, Rhumatologie et Dermatologie pédiatriques, Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de référence de maladies rénales rares, vol.4

, L'étude de formes familiales rares de SN a permis d'identifier des mutations dans de nombreux gènes codant des protéines exprimées par le podocyte. Cependant, dans environ la moitié des cas familiaux de SN, le gène impliqué dans la maladie reste inconnu, et il n'existe à ce jour aucun traitement

. Au-cours-de-ce-travail and . De-recherche, Pour la première partie de mon travail, j'ai travaillé sur deux variants homozygotes identifiés dans les gènes ADD3 et KAT2B chez des enfants présentant un SN associé à une microcéphalie et une cardiomyopathie. Le premier gène code l'adducine-?, un important régulateur du cytosquelette d'actine, et le second pour la lysine acétyltransférase KAT2B responsable de l'acétylation des histones. Mon projet avait pour but d'évaluer la pathogénicité des mutations pour définir leur contribution au phénotype des patients en utilisant le modèle de la Drosophile. J'ai réalisé des expériences d'extinction de l'expression de ces deux gènes, séparément puis simultanément, suivi par des expériences de « sauvetage » pour étudier le phénotype des néphrocytes, équivalents chez la Drosophile des podocytes. Les résultats obtenus ont montré que la mutation d'ADD3 seule n'affecte pas les néphrocytes

. Pour, Le but de ce projet est de comprendre le rôle de la nouvelle sous-unité GON7, une protéine intrinsèquement désordonnée, sur la stabilité du complexe KEOPS, en particulier sur la sous-unité LAGE3 qui interagit directement avec GON7. Nous avons montré que les protéines GON7 et LAGE3 ont une demivie plus courte lorsqu'elles sont exprimées individuellement alors que leur demi-vie augmente lorsqu'elles sont co-exprimées, suggérant que l'interaction stabilise les deux protéines. En parallèle, j'ai développé des modèles murins de « knock-in » (KI) en insérant une mutation dans le gène Osgep ou dans le gène Lage3 par CRISPR/Cas9 afin d'étudier l'effet des mutations sur le développement de l'atteinte rénale et neurologique. Les résultats obtenus à ce jour indiquent que les souris KI ne présentent aucun signe clinique (absence de protéinurie) et histologique évident d'atteinte rénale ou cérébrale