title: Annexin A2 promotes phagophore assembly by enhancing Atg16L⁺ vesicle biogenesis and homotypic fusion.
abstract: Plasma membrane budding of Atg-16L-positive vesicles represents a very early event in the generation of the phagophore and in the process of macroautophagy. Here we show that the membrane curvature-inducing protein annexin A2 contributes to the formation of these vesicles and their fusion to form phagophores. Ultrastructural, proteomic and FACS analyses of Atg16L-positive vesicles reveal that 30% of Atg16L-positive vesicles are also annexin A2-positive. Lipidomic analysis of annexin A2-deficient mouse cells indicates that this protein plays a role in recruiting phosphatidylserine and phosphatidylinositides to Atg16L-positive vesicles. Absence of annexin A2 reduces both vesicle formation and homotypic Atg16L vesicle fusion. Ultimately, a reduction in LC3 flux and dampening of macroautophagy are observed in dendritic cells from Anxa2(-/-) mice. Together, our analyses highlight the importance of annexin A2 in vesiculation of a population of Atg16L-positive structures from the plasma membrane, and in their homotypic fusion to form phagophore structures.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA.
authors.forename: Kateryna
authors.initials: K
authors.lastname: Morozova
authors.affiliation: Department of Developmental Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA.
authors.forename: Sunandini
authors.initials: S
authors.lastname: Sridhar
authors.affiliation: Department of Developmental Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA.
authors.forename: Sunandini
authors.initials: S
authors.lastname: Sidhar
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA.
authors.forename: Valerio
authors.initials: V
authors.lastname: Zolla
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA.
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Clement
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Scharf
authors.affiliation: 1] Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA [2] Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Verzani
authors.affiliation: Department of Developmental Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Diaz
authors.affiliation: Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA.
authors.forename: Jorge N
authors.initials: JN
authors.lastname: Larocca
authors.affiliation: 1] Department of Cell and Developmental Biology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA [2] Department of Pediatrics, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hajjar
authors.affiliation: Department of Developmental Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Cuervo
authors.affiliation: 1] Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA [2] Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Santambrogio
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D010588:Phagosomes / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology
chemical_list: D017306:Annexin A2; D002352:Carrier Proteins