Atg9 establishes Atg2-dependent contact sites between the endoplasmic reticulum and phagophores.

The Journal of Cell Biology
Rubén Gómez-SánchezFulvio Reggiori

Abstract

The autophagy-related (Atg) proteins play a key role in the formation of autophagosomes, the hallmark of autophagy. The function of the cluster composed by Atg2, Atg18, and transmembrane Atg9 is completely unknown despite their importance in autophagy. In this study, we provide insights into the molecular role of these proteins by identifying and characterizing Atg2 point mutants impaired in Atg9 binding. We show that Atg2 associates to autophagosomal membranes through lipid binding and independently from Atg9. Its interaction with Atg9, however, is key for Atg2 confinement to the growing phagophore extremities and subsequent association of Atg18. Assembly of the Atg9-Atg2-Atg18 complex is important to establish phagophore-endoplasmic reticulum (ER) contact sites. In turn, disruption of the Atg2-Atg9 interaction leads to an aberrant topological distribution of both Atg2 and ER contact sites on forming phagophores, which severely impairs autophagy. Altogether, our data shed light in the interrelationship between Atg9, Atg2, and Atg18 and highlight the possible functional relevance of the phagophore-ER contact sites in phagophore expansion.

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Methods Mentioned

BETA
two-hybrid
Y2H
pulldown
immunoprecipitation
pull down
affinity purification
fluorescence microscopy
bimolecular fluorescence complementation
electron microscopy
IET

Software Mentioned

Clustal Omega
Prism
Insight
Illustrator CC
ImageJ
SoftWoRx
IMOD
Photoshop CC
GraphPad
Illustrator

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