Annexin A2 promotes phagophore assembly by enhancing Atg16L⁺ vesicle biogenesis and homotypic fusion.

Autor: Morozova K; Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA., Sridhar S; Department of Developmental Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA., Zolla V; Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA., Clement CC; Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA., Scharf B; Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA., Verzani Z; 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., Diaz A; Department of Developmental Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA., Larocca JN; Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA., Hajjar KA; 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., Cuervo AM; Department of Developmental Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, New York 10461, USA., Santambrogio L; 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.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2015 Jan 19; Vol. 6, pp. 5856. Date of Electronic Publication: 2015 Jan 19.
DOI: 10.1038/ncomms6856
Abstrakt: 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.
Databáze: MEDLINE
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