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

Annexin A2 promotes phagophore assembly by enhancing Atg16L⁺ vesicle biogenesis and homotypic fusion.
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DOI:
10.1038/ncomms6856
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发表时间:
2015-01-19
影响因子:
16.6
通讯作者:
Santambrogio, Laura
Santambrogio, Laura
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Morozova, Kateryna;Sidhar, Sunandini;Zolla, Valerio;Clement, Cristina C.;Scharf, Brian;Verzani, Zoe;Diaz, Antonio;Larocca, Jorge N.;Hajjar, Katherine A.;Cuervo, Ana Maria;Santambrogio, Laura

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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. The earliest steps in autophagy are thought to include the budding of Atg16L-containing vesicles from the plasma membrane and their homotypic fusion to form a phagophore. Morozova et al. reveal a role for the membrane curvature-inducing protein Annexin A2 in the formation and fusion of these vesicles.
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