title: The Bif-1-Dynamin 2 membrane fission machinery regulates Atg9-containing vesicle generation at the Rab11-positive reservoirs.
abstract: Atg9 is a multispanning transmembrane protein that is required for autophagosome formation. During autophagy, vesicles containing Atg9 are generated through an unknown mechanism and delivered to the autophagosome formation sites. We have previously reported that Atg9-containing membranes undergo continuous tubulation and fission during nutrient starvation in a manner dependent on the curvature-inducing protein Bif-1/Sh3glb1. Here, we identify Dynamin 2 (DNM2) as a Bif-1-interacting protein that mediates the fission of Atg9-containing membranes during autophagy. The interaction of Bif-1 and DNM2 is enhanced upon nutrient starvation, and Bif-1 and DNM2 cooperatively induce the generation of Atg9-containing vesicles. Inhibition of the GTPase activity of DNM2 results in the accumulation of Atg9-positive tubular structures that originate from a Rab11-positive reservoir. Although Atg9 seems to be constitutively trafficked to the reservoir regardless of Bif-1 expression, membrane tubulation from the Atg9 reservoir is dependent on Bif-1 and is strongly induced upon nutrient starvation. These findings suggest that the generation of Atg9 vesicles from a Rab11-positive reservoir is tightly controlled by the Bif-1-DNM2 membrane fission machinery in response to cellular demand for autophagy.
authors.affiliation: Department of Pediatrics, Penn State University College of Medicine, Hershey, PA 17033, USA.|Penn State Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Pediatrics, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tsotakos
authors.affiliation: Department of Pharmacology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Young
authors.affiliation: Department of Pharmacology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Serfass
authors.affiliation: Department of Pharmacology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Neural and Behavioral Science and the Microscopy Imaging Facility, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Abraham
authors.affiliation: Department of Pediatrics, Penn State University College of Medicine, Hershey, PA 17033, USA.|Department of Pharmacology, Penn State University College of Medicine, Hershey, PA 17033, USA.|Penn State Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D034285:Dynamin II / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D021381:Protein Transport; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D034285:Dynamin II; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C549015:Atg9A protein, mouse; C429293:SH3GLB1 protein, human
keywords: Atg9 vesicle; Bif-1; Dynamin 2; Rab11-positive reservoir; autophagy