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

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  • Kateryna Morozova

    (Albert Einstein College of Medicine)

  • Sunandini Sidhar

    (Albert Einstein College of Medicine)

  • Valerio Zolla

    (Albert Einstein College of Medicine)

  • Cristina C. Clement

    (Albert Einstein College of Medicine)

  • Brian Scharf

    (Albert Einstein College of Medicine)

  • Zoe Verzani

    (Albert Einstein College of Medicine
    Weill Cornell Medical College)

  • Antonio Diaz

    (Albert Einstein College of Medicine)

  • Jorge N. Larocca

    (Albert Einstein College of Medicine)

  • Katherine A. Hajjar

    (Weill Cornell Medical College
    Weill Cornell Medical College)

  • Ana Maria Cuervo

    (Albert Einstein College of Medicine)

  • Laura Santambrogio

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

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.

Suggested Citation

  • Kateryna Morozova & Sunandini Sidhar & Valerio Zolla & Cristina C. Clement & Brian Scharf & Zoe Verzani & Antonio Diaz & Jorge N. Larocca & Katherine A. Hajjar & Ana Maria Cuervo & Laura Santambrogio, 2015. "Annexin A2 promotes phagophore assembly by enhancing Atg16L+ vesicle biogenesis and homotypic fusion," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6856
    DOI: 10.1038/ncomms6856
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