1. The PIKfyve complex regulates the early melanosome homeostasis required for physiological amyloid formation
- Author
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Guy M. Lenk, Graça Raposo, Lois S. Weisman, Miriam H. Meisler, Wim Annaert, Ilse Hurbain, Emily Kaufman, Ragna Sannerud, Xavier Heiligenstein, Christin Bissig, Guillaume van Niel, Pauline Croisé, Départment of Biochemistry, Université de Genève (UNIGE), Équipe 'Rythme, vie et mort de la rétine', Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Compartimentation et dynamique cellulaires (CDC), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Biology of Myelin Unit, San Raffaele Scientific Institute, Laboratory of Membrane Trafficking and VIB11, Center for Human Genetics, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Department of Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Life Science Institute, Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC)
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BLOC-1 ,SORTING SIGNAL ,[SDV]Life Sciences [q-bio] ,PROTEIN ,Retinal Pigment Epithelium ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Phosphoinositide ,PHOSPHATIDYLINOSITOL 3,5-BISPHOSPHATE ,ACTIN DYNAMICS ,Mice ,Phosphatidylinositol 3-Kinases ,PI(3,5)P-2 ,PIKFYVE ,0302 clinical medicine ,Homeostasis ,LYSOSOMES ,Cells, Cultured ,Mice, Knockout ,0303 health sciences ,Melanosomes ,Intracellular Signaling Peptides and Proteins ,FIG4 ,ENDOSOMES ,Lysosome ,Cell biology ,PMEL ,Protein Transport ,medicine.anatomical_structure ,Melanocytes ,Phosphoinositide Phosphatases ,Life Sciences & Biomedicine ,gp100 Melanoma Antigen ,Melanosome ,Amyloid ,Endosome ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,03 medical and health sciences ,medicine ,Animals ,Actin ,030304 developmental biology ,Science & Technology ,Flavoproteins ,PI(3,5)P2 ,Membrane Proteins ,Correction ,Cell Biology ,PIKfyve ,TRANSPORT ,VAC14 ,Lysosomes ,030217 neurology & neurosurgery ,Biogenesis - Abstract
The metabolism of PI(3,5)P2 is regulated by the PIKfyve, VAC14 and FIG4 complex, mutations in which are associated with hypopigmentation in mice. These pigmentation defects indicate a key, but as yet unexplored, physiological relevance of this complex in the biogenesis of melanosomes. Here, we show that PIKfyve activity regulates formation of amyloid matrix composed of PMEL protein within the early endosomes in melanocytes, called stage I melanosomes. PIKfyve activity controls the membrane remodeling of stage I melanosomes, which regulates PMEL abundance, sorting and processing. PIKfyve activity also affects stage I melanosome kiss-and-run interactions with lysosomes, which are required for PMEL amyloidogenesis and the establishment of melanosome identity. Mechanistically, PIKfyve activity promotes both the formation of membrane tubules from stage I melanosomes and their release by modulating endosomal actin branching. Taken together, our data indicate that PIKfyve activity is a key regulator of the melanosomal import-export machinery that fine tunes the formation of functional amyloid fibrils in melanosomes and the maintenance of melanosome identity.This article has an associated First Person interview with the first author of the paper. ispartof: JOURNAL OF CELL SCIENCE vol:132 issue:5 ispartof: location:England status: published
- Published
- 2019
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