WIPI3 and WIPI4 ß-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy

Bakula, Daniela; Müller, Amelie J.; Zuleger, Theresia; Takacs, Zsuzsanna; Franz-Wachtel, Mirita; Thost, Ann-Katrin; Brigger, Daniel; Tschan, Mario P.; Frickey, Tancred; Robenek, Horst; Macek, Boris; Proikas-Cezanne, Tassula

WIPI3 and WIPI4 ß-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy

Dateien

Bakula_0-411080.pdfGröße: 4.55 MBDownloads: 902

Datum

2017

Autor:innen

Bakula, Daniela

Müller, Amelie J.

Zuleger, Theresia

Takacs, Zsuzsanna

Franz-Wachtel, Mirita

Thost, Ann-Katrin

Brigger, Daniel

Tschan, Mario P.

Frickey, Tancred

Robenek, Horst

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Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Nature Communications. 2017, 8, 15637. eISSN 2041-1723. Available under: doi: 10.1038/ncomms15637

Zusammenfassung

Autophagy is controlled by AMPK and mTOR, both of which associate with ULK1 and control the production of phosphatidylinositol 3-phosphate (PtdIns3P), a prerequisite for autophagosome formation. Here we report that WIPI3 and WIPI4 scaffold the signal control of autophagy upstream of PtdIns3P production and have a role in the PtdIns3P effector function of WIPI1-WIPI2 at nascent autophagosomes. In response to LKB1-mediated AMPK stimulation, WIPI4-ATG2 is released from a WIPI4-ATG2/AMPK-ULK1 complex and translocates to nascent autophagosomes, controlling their size, to which WIPI3, in complex with FIP200, also contributes. Upstream, WIPI3 associates with AMPK-activated TSC complex at lysosomes, regulating mTOR. Our WIPI interactome analysis reveals the scaffold functions of WIPI proteins interconnecting autophagy signal control and autophagosome formation. Our functional kinase screen uncovers a novel regulatory link between LKB1-mediated AMPK stimulation that produces a direct signal via WIPI4, and we show that the AMPK-related kinases NUAK2 and BRSK2 regulate autophagy through WIPI4.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

BAKULA, Daniela, Amelie J. MÜLLER, Theresia ZULEGER, Zsuzsanna TAKACS, Mirita FRANZ-WACHTEL, Ann-Katrin THOST, Daniel BRIGGER, Mario P. TSCHAN, Tancred FRICKEY, Horst ROBENEK, Boris MACEK, Tassula PROIKAS-CEZANNE, 2017. WIPI3 and WIPI4 ß-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. In: Nature Communications. 2017, 8, 15637. eISSN 2041-1723. Available under: doi: 10.1038/ncomms15637

BibTex

@article{Bakula2017WIPI3-39501,
  year={2017},
  doi={10.1038/ncomms15637},
  title={WIPI3 and WIPI4 ß-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy},
  volume={8},
  journal={Nature Communications},
  author={Bakula, Daniela and Müller, Amelie J. and Zuleger, Theresia and Takacs, Zsuzsanna and Franz-Wachtel, Mirita and Thost, Ann-Katrin and Brigger, Daniel and Tschan, Mario P. and Frickey, Tancred and Robenek, Horst and Macek, Boris and Proikas-Cezanne, Tassula},
  note={Article Number: 15637}
}

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Universitätsbibliographie

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