title: Myelinosomes act as natural secretory organelles in Sertoli cells to prevent accumulation of aggregate-prone mutant Huntingtin and CFTR.
abstract: Inappropriate deposition of insoluble aggregates of proteins with abnormal structures is a hallmark of affected organs in protein aggregation disease. Very rare, affected organs avoid aggregation naturally. This concerns atrophic testis in Huntington disease (HD). We aimed to understand how HD testis avoids aggregation. Using HD model R6/1 mice, we demonstrate that affected testis contain rare organelles myelinosomes. Myelinosomes secreted from testis somatic TM4 Sertoli cells provide the release of aggregate-prone mutant, but not normal Huntingtin (Htt) exon1. Myelinosomes also support the release of other aggregate-prone mutant protein responsible for cystic fibrosis (CF), F508delCFTR. The traffic and discharge of myelinosomes is facilitated by multivesicular bodies (MVB)s. Inhibition of MVB excretion induced reversible retention of both misfolded proteins inside TM4 Sertoli cells. We propose that myelinosome-mediated elimination of mutant proteins is an unusual secretory process allowing Sertoli cells getting rid of misfolded proteins to avoid aggregation and to maintain cell proteostasis.
authors: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers/CNRS, 1 rue Georges Bonnet, F-86022 Poitiers, France.|Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44, Prosp. Maurice Thorez, St Petersbourg 194233, Russian Federation.
authors: Marina G
authors: MG
authors: Yefimova
authors: Plateforme IMAGE-UP, 1 rue Georges Bonnet, F-86022 Poitiers, France.
authors: Emile
authors: E
authors: Béré
authors: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers/CNRS, 1 rue Georges Bonnet, F-86022 Poitiers, France.|Plateforme IMAGE-UP, 1 rue Georges Bonnet, F-86022 Poitiers, France.
authors: Anne
authors: A
authors: Cantereau-Becq
authors: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers/CNRS, 1 rue Georges Bonnet, F-86022 Poitiers, France.
authors: Thomas
authors: T
authors: Harnois
authors: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers/CNRS, 1 rue Georges Bonnet, F-86022 Poitiers, France.
authors: Annie-Claire
authors: AC
authors: Meunier
authors: Institute of Genetics and Molecular and Cellular Biology, 67404 Illkirch, France.|Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France.|Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France.|Université de Strasbourg, 67000 Strasbourg, France.
authors: Nadia
authors: N
authors: Messaddeq
authors: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers/CNRS, 1 rue Georges Bonnet, F-86022 Poitiers, France.
authors: Frédéric
authors: F
authors: Becq
authors: Institute of Genetics and Molecular and Cellular Biology, 67404 Illkirch, France.|Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France.|Institut National de la Santé et de la Recherche Médicale, U964, 67404 Illkirch, France.|Université de Strasbourg, 67000 Strasbourg, France.
authors: Yvon
authors: Y
authors: Trottier
authors: Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers/CNRS, 1 rue Georges Bonnet, F-86022 Poitiers, France n.bourmeyster@chu-poitiers.fr.|CHU de Poitiers, 86022, Poitiers Cedex, France.
authors: Nicolas
authors: N
authors: Bourmeyster
mesh_terms: D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics*; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR; D050505:Mutant Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D015388:Organelles / Q000235:genetics / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000235:genetics*; D012708:Sertoli Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D050505:Mutant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator