Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells

• Published in: Cell reports (Cambridge) Vol. 13; no. 1; pp. 43 - 51
• Main Authors: van Niel, Guillaume, Bergam, Ptissam, Di Cicco, Aurelie, Hurbain, Ilse, Lo Cicero, Alessandra, Dingli, Florent, Palmulli, Roberta, Fort, Cecile, Potier, Marie Claude, Schurgers, Leon J., Loew, Damarys, Levy, Daniel, Raposo, Graça
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.10.2015; Elsevier
• Subjects: Amyloid - genetics; Amyloid - metabolism; Amyloid - ultrastructure; Animals; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Cellular Biology; Endosomal Sorting Complexes Required for Transport - genetics; Endosomal Sorting Complexes Required for Transport - metabolism; Endosomes - metabolism; Endosomes - ultrastructure; Exosomes - metabolism; Exosomes - ultrastructure; Gene Expression Regulation; HeLa Cells; Humans; Life Sciences; Melanocytes - metabolism; Melanocytes - ultrastructure; Melanosomes - metabolism; Melanosomes - ultrastructure; Mice; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.08.057

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. [Display omitted] •Exosomes and endosomal intraluminal vesicles are associated with ApoE•ApoE regulates the formation of PMEL amyloid fibrils in endosomes•ApoE supports the ESCRT independent sorting of PMEL to ILVs Amyloids are protein aggregates that can be cytotoxic. van Niel et al. showed that Apolipoprotein E, a key factor involved in the metabolism of these pathological amyloids, regulates the formation in a non-toxic manner of amyloid structures that serves physiological functions in specialized cells.