Atg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction.
Under normal growth conditions the mammalian target of rapamycin complex 1 (mTORC1) negatively regulates the central autophagy regulator complex consisting of Unc-51-like kinases 1/2 (Ulk1/2), focal adhesion kinase family-interacting protein of 200 kDa (FIP200) and Atg13. Upon starvation, mTORC1-mediated repression of this complex is released, which then leads to Ulk1/2 activation. In this scenario, Atg13 has been proposed as an adaptor mediating the interaction between Ulk1/2 and FIP200 and enhancing Ulk1/2 kinase activity. Using Atg13-deficient cells, we demonstrate that Atg13 is indispensable for autophagy induction. We further show that Atg13 function strictly depends on FIP200 binding. In contrast, the simultaneous knockout of Ulk1 and Ulk2 did not have a similar effect on autophagy induction. Accordingly, the Ulk1-dependent phosphorylation sites we identified in Atg13 are expendable for this process. This suggests that Atg13 has an additional function independent of Ulk1/2 and that Atg13 and FIP200 act in concert during autophagy induction.
Department of Internal Medicine I; University Clinic of Tübingen; Tübingen, Germany.
Sebastian
S
Alers
Antje S
AS
Löffler
Florian
F
Paasch
Alexandra M
AM
Dieterle
Hildegard
H
Keppeler
Kirsten
K
Lauber
David G
DG
Campbell
Birgit
B
Fehrenbacher
Martin
M
Schaller
Sebastian
S
Wesselborg
Björn
B
Stork
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D001665:Binding Sites; D002460:Cell Line; D002645:Chickens; D005091:Exons / Q000235:genetics; D055786:Gene Knockout Techniques; D008954:Models, Biological; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases