title: Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells.
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.
authors.affiliation: 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: guillaume.van-niel@curie.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: van Niel
authors.affiliation: 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.
authors.forename: Ptissam
authors.initials: P
authors.lastname: Bergam
authors.affiliation: 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.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Di Cicco
authors.affiliation: 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.
authors.forename: Ilse
authors.initials: I
authors.lastname: Hurbain
authors.affiliation: 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.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lo Cicero
authors.affiliation: Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, Paris 75248, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Dingli
authors.affiliation: 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.
authors.forename: Roberta
authors.initials: R
authors.lastname: Palmulli
authors.affiliation: 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.
authors.forename: Cecile
authors.initials: C
authors.lastname: Fort
authors.affiliation: 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.
authors.forename: Marie Claude
authors.initials: MC
authors.lastname: Potier
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Schurgers
authors.affiliation: Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, Paris 75248, France.
authors.forename: Damarys
authors.initials: D
authors.lastname: Loew
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.affiliation: 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.
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
mesh_terms: D000682:Amyloid / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D055354:Exosomes / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008544:Melanocytes / Q000378:metabolism* / Q000648:ultrastructure; D020460:Melanosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction
chemical_list: D000682:Amyloid; D001057:Apolipoproteins E; D056827:Endosomal Sorting Complexes Required for Transport