Annexin A2 promotes phagophore assembly by enhancing Atg16L⺠vesicle biogenesis and homotypic fusion.
Nat Commun
; 6: 5856, 2015 Jan 19.
Article
em En
| MEDLINE
| ID: mdl-25597631
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Membrana Celular
/
Anexina A2
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article