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

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

doi:10.1038/ncomms6856

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

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

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33 Scopus citations

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.

Original language	English (US)
Article number	5856
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms6856
State	Published - Jan 2015

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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@article{16339159e5e247f292b527b724a3ae72,

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.",

author = "Kateryna Morozova and Sunandini Sidhar and Valerio Zolla and Clement, {Cristina C.} and Brian Scharf and Zoe Verzani and Antonio Diaz and Larocca, {Jorge N.} and Hajjar, {Katherine A.} and Cuervo, {Ana Maria} and Laura Santambrogio",

note = "Funding Information: This work was supported by the National Institutes of Health Grant AG031782 to A.M.C., and L.S. and HL042493 to KAH. We acknowledge Edward Nieves and the Laboratory for Macromolecular Analysis and Proteomic at Albert Einstein College of Medicine (NIH grant 1S10RR019352) and MS-Bioworks (Ann Arbor, MI) for the mass spectrometry services. We gratefully acknowledge the expert technical assistance of Dena Almeida. V.Z. is supported by the PhD programme in Genetics and Cell Biology at the University of Tuscia, Department of Ecology and Biology (DEB), Viterbo, Italy. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",

year = "2015",

month = jan,

doi = "10.1038/ncomms6856",

language = "English (US)",

volume = "6",

journal = "Nature communications",

issn = "2041-1723",

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T1 - Annexin A2 promotes phagophore assembly by enhancing Atg16L+ vesicle biogenesis and homotypic fusion

AU - Morozova, Kateryna

AU - Sidhar, Sunandini

AU - Zolla, Valerio

AU - Clement, Cristina C.

AU - Scharf, Brian

AU - Verzani, Zoe

AU - Diaz, Antonio

AU - Larocca, Jorge N.

AU - Hajjar, Katherine A.

AU - Cuervo, Ana Maria

AU - Santambrogio, Laura

N1 - Funding Information: This work was supported by the National Institutes of Health Grant AG031782 to A.M.C., and L.S. and HL042493 to KAH. We acknowledge Edward Nieves and the Laboratory for Macromolecular Analysis and Proteomic at Albert Einstein College of Medicine (NIH grant 1S10RR019352) and MS-Bioworks (Ann Arbor, MI) for the mass spectrometry services. We gratefully acknowledge the expert technical assistance of Dena Almeida. V.Z. is supported by the PhD programme in Genetics and Cell Biology at the University of Tuscia, Department of Ecology and Biology (DEB), Viterbo, Italy. Publisher Copyright: © 2015 Macmillan Publishers Limited. All rights reserved.

PY - 2015/1

Y1 - 2015/1

N2 - 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.

AB - 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.

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JO - Nature communications

JF - Nature communications

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

Abstract

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