PMEL: a pigment cell‐specific model for functional amyloid formation |
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Authors: | Brenda Watt Guillaume van Niel Graça Raposo Michael S. Marks |
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Affiliation: | 1. Department of Pathology and Laboratory Medicine, Department of Physiology, and Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, , Philadelphia, PA, USA;2. Institut Curie, Centre de Recherche, , Paris, France;3. Structure and Membrane Compartments, Centre National de la Recherche Scientifique, UMR144, , Paris, France |
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Abstract: | PMEL is a pigment cell‐specific protein responsible for the formation of fibrillar sheets within the pigment organelle, the melanosome. The fibrillar sheets serve as a template upon which melanins polymerize as they are synthesized. The PMEL fibrils are required for optimal pigment cell function, as animals that either lack PMEL expression or express mutant PMEL variants show varying degrees of hypopigmentation and pigment cell inviability. The PMEL fibrils have biophysical properties of amyloid, a protein fold that is frequently associated with neurodegenerative and other diseases. However, PMEL is one of a growing number of non‐pathogenic amyloid proteins that contribute to the function of the cell and/or organism that produces them. Understanding how PMEL generates amyloid in a non‐pathogenic manner might provide insights into how to avoid toxicity due to pathological amyloid formation. In this review, we summarize and reconcile data concerning the fate of PMEL from its site of synthesis in the endoplasmic reticulum to newly formed melanosomes and the role of distinct PMEL subdomains in trafficking and amyloid fibril formation. We then discuss how its progression through the secretory pathway into the endosomal system might allow for the regulated and non‐toxic conversion of PMEL into an ordered amyloid polymer. |
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Keywords: | Pmel17 Silver multivesicular body melanosome fibrils Alzheimer Disease proprotein processing |
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