title: Scaffolding the expansion of autophagosomes.
abstract: The conjugation of the small ubiquitin (Ub)-like protein Atg8 to autophagic membranes is a key step during the expansion of phagophores. This reaction is driven by 2 interconnected Ub-like conjugation systems. The second system conjugates the Ub-like protein Atg12 to Atg5. The resulting conjugate catalyzes the covalent attachment of Atg8 to membranes. Atg12-Atg5, however, constitutively associates with the functionally less well-characterized coiled-coil protein Atg16. By reconstituting the conjugation of Atg8 to membranes in vitro, we showed that after Atg8 has been attached to phosphatidylethanolamine (PE), it recruits Atg12-Atg5 to membranes by recognizing a noncanonical Atg8-interacting motif (AIM) within Atg12. Atg16 crosslinks Atg8-PE-Atg12-Atg5 complexes to form a continuous 2-dimensional membrane scaffold with meshwork-like architecture. Apparently, scaffold formation is required to generate productive autophagosomes and to deliver autophagic cargo to the vacuole in vivo.
authors: Molecular Membrane and Organelle Biology; Max Planck Institute of Biochemistry; Martinsried, Germany.
authors: Anna
authors: A
authors: Kaufmann
authors: Molecular Membrane and Organelle Biology; Max Planck Institute of Biochemistry; Martinsried, Germany.
authors: Thomas
authors: T
authors: Wollert
mesh_terms: D000818:Animals; D001343:Autophagy; D002462:Cell Membrane / Q000378:metabolism*; D008840:Microfilament Proteins; D008954:Models, Biological; D010588:Phagosomes / Q000378:metabolism*
chemical_list: D008840:Microfilament Proteins
keywords: Atg8; conjugation; macroautophagy; membrane scaffold; reconstitution