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

Hum Mol Genet. 2016 Oct 1;25(19):4170-4185. doi: 10.1093/hmg/ddw251. Epub 2016 Aug 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Humans
  • Huntingtin Protein / genetics*
  • Huntington Disease / genetics*
  • Huntington Disease / metabolism
  • Huntington Disease / pathology
  • Male
  • Mice
  • Mice, Inbred CFTR
  • Mutant Proteins / genetics
  • Neurons / metabolism
  • Neurons / pathology
  • Organelles / genetics
  • Organelles / metabolism
  • Protein Aggregation, Pathological / genetics*
  • Sertoli Cells / metabolism
  • Sertoli Cells / pathology


  • HTT protein, human
  • Huntingtin Protein
  • Mutant Proteins
  • Cystic Fibrosis Transmembrane Conductance Regulator