title: PMEL Amyloid Fibril Formation: The Bright Steps of Pigmentation.
abstract: In pigment cells, melanin synthesis takes place in specialized organelles, called melanosomes. The biogenesis and maturation of melanosomes is initiated by an unpigmented step that takes place prior to the initiation of melanin synthesis and leads to the formation of luminal fibrils deriving from the pigment cell-specific pre-melanosomal protein (PMEL). In the lumen of melanosomes, PMEL fibrils optimize sequestration and condensation of the pigment melanin. Interestingly, PMEL fibrils have been described to adopt a typical amyloid-like structure. In contrast to pathological amyloids often associated with neurodegenerative diseases, PMEL fibrils represent an emergent category of physiological amyloids due to their beneficial cellular functions. The formation of PMEL fibrils within melanosomes is tightly regulated by diverse mechanisms, such as PMEL traffic, cleavage and sorting. These mechanisms revealed increasing analogies between the formation of physiological PMEL fibrils and pathological amyloid fibrils. In this review we summarize the known mechanisms of PMEL fibrillation and discuss how the recent understanding of physiological PMEL amyloid formation may help to shed light on processes involved in pathological amyloid formation.
authors: Institut Curie, Paris Sciences et Lettres Research University, UMR144, Centre de Recherche, 26 rue d'ULM, Paris F-75231, France. christin.bissig@curie.fr.|Centre National de la Recherche Scientifique, UMR144, Paris F-75248, France. christin.bissig@curie.fr.
authors: Christin
authors: C
authors: Bissig
authors: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK. Leila.Rochin@liverpool.ac.uk.
authors: Leila
authors: L
authors: Rochin
authors: Institut Curie, Paris Sciences et Lettres Research University, UMR144, Centre de Recherche, 26 rue d'ULM, Paris F-75231, France. guillaume.van-niel@curie.fr.|Centre National de la Recherche Scientifique, UMR144, Paris F-75248, France. guillaume.van-niel@curie.fr.
authors: Guillaume
authors: G
authors: van Niel
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D006801:Humans; D020460:Melanosomes / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D012880:Skin Pigmentation; D058951:gp100 Melanoma Antigen / Q000378:metabolism*
chemical_list: D000682:Amyloid; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen
keywords: PMEL; amyloid; apolipoprotein E; fibril formation; melanocyte; melanosome; pigmentation; secretases