1. PIKfyve activity regulates reformation of terminal storage lysosomes from endolysosomes
- Author
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Bissig, Christin, Croise, Pauline, Heiligenstein, Xavier, Hurbain, Ilse, Lenk, Guy, Kaufman, Emily, Sannerud, Ragna, Annaert, Wim, Meisler, Miriam, Weisman, Lois, Raposo, Graça, van Niel, Guillaume, Université de Lausanne = University of Lausanne (UNIL), 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), 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 de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm - Paris Descartes), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), van Niel, Guillaume, and Université de Lausanne (UNIL)
- Subjects
0301 basic medicine ,Scaffold protein ,lysosome reformation ,Endosome ,Endocytic cycle ,Phosphatase ,Cell Culture Techniques ,electron tomography ,Endosomes ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Biology ,PtdIns (3 5)P2 ,Biochemistry ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,chemistry.chemical_compound ,PIKFYVE ,0302 clinical medicine ,Structural Biology ,Lysosome ,Genetics ,medicine ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Homeostasis ,Humans ,Phosphatidylinositol ,Molecular Biology ,Flavoproteins ,Intracellular Signaling Peptides and Proteins ,Membrane Proteins ,Cell Biology ,phosphoinositides ,FIG4 ,PIKfyve ,Endolysosome ,Phosphoric Monoester Hydrolases ,Cell biology ,endolysosome ,Microscopy, Electron ,Protein Transport ,030104 developmental biology ,medicine.anatomical_structure ,Microscopy, Fluorescence ,chemistry ,VAC14 ,Lysosomes ,030217 neurology & neurosurgery ,HeLa Cells - Abstract
International audience; The protein complex composed of the kinase PIKfyve, the phosphatase FIG4 and the scaffolding protein VAC14 regulates the metabolism of phosphatidylinositol 3,5-bisphosphate, which serves as both a signaling lipid and the major precursor for phosphatidylinositol 5-phosphate. This complex is involved in the homeostasis of late endocytic compartments, but its precise role in maintaining the dynamic equilibrium of late endosomes, endolysosomes and lysosomes remains to be determined. Here, we report that inhibition of PIKfyve activity impairs terminal lysosome reformation from acidic and hydrolase-active, but enlarged endolysosomes. Our live-cell imaging and electron tomography data show that PIKfyve activity regulates extensive membrane remodeling that initiates reformation of lysosomes from endolysosomes. Altogether, our findings show that PIKfyve activity is required to maintain the dynamic equilibrium of late endocytic compartments by regulating the reformation of terminal storage lysosomes. K E Y W O R D S electron tomography, endolysosome, FIG4, lysosome reformation, phosphoinositides, PtdIns (3,5)P2, PIKfyve, VAC14
- Published
- 2017