Myelinosomes act as natural secretory organelles in Sertoli cells to prevent accumulation of aggregate-prone mutant Huntingtin and CFTR.
Fiche publication
Date publication
octobre 2016
Journal
Human molecular genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Mme MESSADDEQ Nadia
Tous les auteurs :
Yefimova MG, Béré E, Cantereau-Becq A, Harnois T, Meunier AC, Messaddeq N, Becq F, Trottier Y, Bourmeyster N
Lien Pubmed
Résumé
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.
Mots clés
Animals, Cystic Fibrosis Transmembrane Conductance Regulator, genetics, Humans, Huntingtin Protein, genetics, Huntington Disease, genetics, Male, Mice, Mice, Inbred CFTR, Mutant Proteins, genetics, Neurons, metabolism, Organelles, genetics, Protein Aggregation, Pathological, genetics, Sertoli Cells, metabolism
Référence
Hum. Mol. Genet.. 2016 10 1;25(19):4170-4185