title: Membrane morphology is actively transformed by covalent binding of the protein Atg8 to PE-lipids.
abstract: Autophagy is a cellular degradation pathway involving the shape transformation of lipid bilayers. During the onset of autophagy, the water-soluble protein Atg8 binds covalently to phosphatdylethanolamines (PEs) in the membrane in an ubiquitin-like reaction coupled to ATP hydrolysis. We reconstituted the Atg8 conjugation system in giant and nm-sized vesicles with a minimal set of enzymes and observed that formation of Atg8-PE on giant vesicles can cause substantial tubulation of membranes even in the absence of Atg12-Atg5-Atg16. Our findings show that ubiquitin-like processes can actively change properties of lipid membranes and that membrane crowding by proteins can be dynamically regulated in cells. Furthermore we provide evidence for curvature sorting of Atg8-PE. Curvature generation and sorting are directly linked to organelle shapes and, thus, to biological function. Our results suggest that a positive feedback exists between the ubiquitin-like reaction and the membrane curvature, which is important for dynamic shape changes of cell membranes, such as those involved in the formation of autophagosomes.
authors.affiliation: Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Roland L
authors.initials: RL
authors.lastname: Knorr
authors.affiliation: Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakatogawa
authors.affiliation: Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohsumi
authors.affiliation: Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lipowsky
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Tobias
authors.initials: T
authors.lastname: Baumgart
authors.affiliation: Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Rumiana
authors.initials: R
authors.lastname: Dimova
mesh_terms: D000071190:Autophagy-Related Protein 8 Family; D008081:Liposomes / Q000378:metabolism / Q000648:ultrastructure*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D008081:Liposomes; D008869:Microtubule-Associated Proteins; D010714:Phosphatidylethanolamines; D029701:Saccharomyces cerevisiae Proteins