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Article Dans Une Revue Human Molecular Genetics Année : 2016

Myelinosomes act as natural secretory organelles in Sertoli cells to prevent accumulation of aggregate-prone mutant Huntingtin and CFTR

Marina G. Yefimova
  • Fonction : Auteur
Emile Béré
  • Fonction : Auteur
Anne Cantereau-Becq
Thomas Harnois
Annie-Claire Meunier
  • Fonction : Auteur
Frédéric Becq
Nicolas Bourmeyster

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.

Dates et versions

hal-03686913 , version 1 (02-06-2022)

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Citer

Marina G. Yefimova, Emile Béré, Anne Cantereau-Becq, Thomas Harnois, Annie-Claire Meunier, et al.. Myelinosomes act as natural secretory organelles in Sertoli cells to prevent accumulation of aggregate-prone mutant Huntingtin and CFTR. Human Molecular Genetics, 2016, 25 (19), pp.4170-4185. ⟨10.1093/hmg/ddw251⟩. ⟨hal-03686913⟩
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