Inter-organelle lipid transfer: a channel model for Vps13 and chorein-N motif proteins |
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| Affiliation: | 1. Cellular Dynamics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan;2. Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan;3. Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA;1. Sorbonne Universités, UPMC Université Paris 6 UMR S 1127, 75013 Paris, France;2. Inserm U 1127, 75013 Paris, France;3. CNRS UMR 7225, 75013 Paris, France;4. Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, France;5. Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA;6. Department of Histology and Pathology, University of Lille Nord de France, Lille University Hospital, 59000 Lille, France;7. Centre d’Investigation Clinique Pitié Neurosciences CIC-1422, 75013 Paris, France;8. Fondation Jean Dausset-CEPH, 75010 Paris, France;9. Institute of Neuroanatomy, Eberhard Karls University Tübingen, 72074 Tübingen, Germany;10. Behavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey;11. Department of Genetics, Institute for Experimental Medicine, Istanbul University, 34390 Istanbul, Turkey;12. Institut des Maladies Neurodégénératives, Université de Bordeaux et CHU de Bordeaux, 33000 Bordeaux, France;13. Pôle Tête-Cou-CETD, Service de Neurologie, Hôpitaux Universitaires, 67000 Strasbourg, France;14. Pôle des Maladies du Système Nerveux, Fédération de Neurologie, Hôpital de la Salpêtrière, 75013 Paris, France;15. Neurology Department, CHU de Grenoble, Joseph Fourier University, and INSERM U836, 38000 Grenoble, France;16. Inserm U946, 75010 Paris, France;17. Université Paris Diderot, Institut Universitaire d’Hématologie, UMR946, 75010 Paris, France;18. Hertie Institute for Clinical Brain Research, University of Tübingen and DZNE, German Center for Neurodegenerative Diseases, 72074 Tübingen, Germany;19. Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK;20. Department of Genetics and Cytogenetics, AP-HP, Hôpital de la Salpêtrière, 75013 Paris, France;21. Commissariat à l’Energie Atomique, Institut Génomique, Centre National de Génotypage, 91000 Evry, France;22. Service de Neurologie CHU Mustapha, 16000 Alger, Algérie;23. Movement Disorders Unit, Lille University, Inserm U837, Lille University Hospital, 59000 Lille, France;24. Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, 72076 Tübingen, Germany;1. UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, UK;1. Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA;2. Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA;3. Institute for Genetics, University of Cologne, 50674 Cologne, Germany;1. Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany;2. Institute of Neuropathology, University Medical Center Göttingen, Göttingen 37099, Germany;3. Graduate School of Quantitative Biosciences Munich, Munich 81337, Germany;4. ICFO, Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Castelldefels 08860, Spain;5. Department of Molecular Biology, University of Geneva, Geneva 1211, Switzerland;6. MRC Laboratory for Molecular Cell Biology, University College London, London, WC1E 6BT, UK;7. Swiss National Centre for Competence in Research, Program Chemical Biology, Geneva 1211, Switzerland;8. Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Göttingen, Germany |
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| Abstract: | Membrane contact sites, where two organelles are in close proximity, are critical regulators of cellular membrane homeostasis, with roles in signaling, lipid metabolism, and ion dynamics. A growing catalog of specialized lipid transfer proteins carry out lipid exchange at these sites. Currently characterized eukaryotic lipid transport proteins are shuttles that typically extract a single lipid from the membrane of the donor organelle, solubilize it during transport through the cytosol, and deposit it in the acceptor organelle membrane. Here, we highlight the recently identified chorein_N family of lipid transporters, including the Vps13 proteins and the autophagy protein Atg2. These are elongated proteins that, distinct from previously characterized transport proteins, bind tens of lipids at once. They feature an extended channel, most likely lined with hydrophobic residues. We discuss the possibility that they are not shuttles but instead are bridges between membranes, with lipids traversing the cytosol via the hydrophobic channel. |
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| Keywords: | Membrane contact sites Lipid transfer proteins Chorein_N motif |
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