First Author | Morozova K | Year | 2015 |
Journal | Nat Commun | Volume | 6 |
Pages | 5856 | PubMed ID | 25597631 |
Mgi Jnum | J:219726 | Mgi Id | MGI:5629623 |
Doi | 10.1038/ncomms6856 | Citation | Morozova K, et al. (2015) Annexin A2 promotes phagophore assembly by enhancing Atg16L(+) vesicle biogenesis and homotypic fusion. Nat Commun 6:5856 |
abstractText | 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. |