Prelysosomal Compartments in the Unconventional Secretion of Amyloidogenic Seeds

Helena Borland, Frederik Vilhardt

Research output: Contribution to journalReviewResearchpeer-review

21 Citations (Scopus)
187 Downloads (Pure)

Abstract

A mechanistic link between neuron-to-neuron transmission of secreted amyloid and propagation of protein malconformation cytopathology and disease has recently been uncovered in animal models. An enormous interest in the unconventional secretion of amyloids from neurons has followed. Amphisomes and late endosomes are the penultimate maturation products of the autophagosomal and endosomal pathways, respectively, and normally fuse with lysosomes for degradation. However, under conditions of perturbed membrane trafficking and/or lysosomal deficiency, prelysosomal compartments may instead fuse with the plasma membrane to release any contained amyloid. After a brief introduction to the endosomal and autophagosomal pathways, we discuss the evidence for autophagosomal secretion (exophagy) of amyloids, with a comparative emphasis on Aβ1-42 and α-synuclein, as luminal and cytosolic amyloids, respectively. The ESCRT-mediated import of cytosolic amyloid into late endosomal exosomes, a known vehicle of transmission of macromolecules between cells, is also reviewed. Finally, mechanisms of lysosomal dysfunction, deficiency, and exocytosis are exemplified in the context of genetically identified risk factors, mainly for Parkinson's disease. Exocytosis of prelysosomal or lysosomal organelles is a last resort for clearance of cytotoxic material and alleviates cytopathy. However, they also represent a vehicle for the concentration, posttranslational modification, and secretion of amyloid seeds.

Original languageEnglish
Article number227
JournalInternational Journal of Molecular Sciences (Online)
Volume18
Issue number1
ISSN1661-6596
DOIs
Publication statusPublished - 2017

Keywords

  • Amyloid
  • Animals
  • Autophagy
  • Cell Compartmentation
  • Endosomes
  • Humans
  • Lysosomes
  • alpha-Synuclein
  • Journal Article
  • Review

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