2. Academic Validation
  3. Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells

Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells

  • Cell Rep. 2015 Oct 6;13(1):43-51. doi: 10.1016/j.celrep.2015.08.057.
Guillaume van Niel 1,  Ptissam Bergam 2,  Aurelie Di Cicco 3,  Ilse Hurbain 2,  Alessandra Lo Cicero 4,  Florent Dingli 5,  Roberta Palmulli 4,  Cecile Fort 4,  Marie Claude Potier 6,  Leon J Schurgers 7,  Damarys Loew 5,  Daniel Levy 3,  Graça Raposo 2
Affiliations

Affiliations

  • 1 Institut Curie, PSL Research University, UMR144, Centre de Recherche, 26 rue d'ULM, Paris 75231, France; Centre National de la Recherche Scientifique, UMR144, Paris 75248, France; Cell and Tissue Imaging Core Facility PICT-IBiSA, Institut Curie, Paris 75248, France. Electronic address: [email protected].
  • 2 Institut Curie, PSL Research University, UMR144, Centre de Recherche, 26 rue d'ULM, Paris 75231, France; Centre National de la Recherche Scientifique, UMR144, Paris 75248, France; Cell and Tissue Imaging Core Facility PICT-IBiSA, Institut Curie, Paris 75248, France.
  • 3 Cell and Tissue Imaging Core Facility PICT-IBiSA, Institut Curie, Paris 75248, France; Institut Curie, PSL Research University, UMR168, Centre de Recherche, 26 rue d'ULM, Paris 75231, France; Centre National de la Recherche Scientifique, UMR 168, Paris 75231, France.
  • 4 Institut Curie, PSL Research University, UMR144, Centre de Recherche, 26 rue d'ULM, Paris 75231, France; Centre National de la Recherche Scientifique, UMR144, Paris 75248, France.
  • 5 Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, Paris 75248, France.
  • 6 Institut du Cerveau et de la Moelle, CNRS UMR7225, INSERM U1127, UPMC Hôpital de la Pitié-Salpêtrière, 47 Bd de l'Hôpital, Paris 75013, France.
  • 7 Department of Biochemistry, Cardiovascular Research Institute Maastricht, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
PMID: 26387950 DOI: 10.1016/j.celrep.2015.08.057
Abstract

Accumulation of toxic amyloid oligomers is a key feature in the pathogenesis of amyloid-related diseases. Formation of mature amyloid fibrils is one defense mechanism to neutralize toxic prefibrillar oligomers. This mechanism is notably influenced by apolipoprotein E variants. Cells that produce mature amyloid fibrils to serve physiological functions must exploit specific mechanisms to avoid potential accumulation of toxic species. Pigment cells have tuned their endosomes to maximize the formation of functional amyloid from the protein PMEL. Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. ApoE functions in the ESCRT-independent sorting mechanism of PMEL onto ILVs and regulates the endosomal formation of PMEL amyloid fibrils in vitro and in vivo. This process secures the physiological formation of amyloid fibrils by exploiting ILVs as amyloid nucleating platforms.

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