WIPI3 and WIPI4 ß-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy
| العنوان: | WIPI3 and WIPI4 ß-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy |
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| المؤلفون: | Tancred Frickey, Daniela Bakula, Zsuzsanna Takacs, Amelie J. Müller, Mario P. Tschan, Ann-Katrin Thost, Daniel Brigger, Mirita Franz-Wachtel, Theresia Zuleger, Boris Macek, Tassula Proikas-Cezanne, Horst Robenek |
| المصدر: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-18 (2017) Bakula, Daniela; Müller, Amelie J; Zuleger, Theresia; Takacs, Zsuzsanna; Franz-Wachtel, Mirita; Thost, Ann-Katrin; Brigger, Daniel; Tschan, Mario; Frickey, Tancred; Robenek, Horst; Macek, Boris; Proikas-Cezanne, Tassula (2017). WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. Nature communications, 8(15637), p. 15637. Nature Publishing Group 10.1038/ncomms15637 <http://dx.doi.org/10.1038/ncomms15637Test> |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Protein Conformation, Science, Vesicular Transport Proteins, General Physics and Astronomy, Autophagy-Related Proteins, 610 Medicine & health, Biology, AMP-Activated Protein Kinases, Protein Serine-Threonine Kinases, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, AMP-Activated Protein Kinase Kinases, Phosphatidylinositol Phosphates, Cell Line, Tumor, Phagosomes, ddc:570, Autophagy, Autophagy-Related Protein-1 Homolog, Humans, PI3K/AKT/mTOR pathway, Adaptor Proteins, Signal Transducing, Multidisciplinary, Effector, Kinase, Intracellular Signaling Peptides and Proteins, AMPK, Signal transducing adaptor protein, General Chemistry, ULK1, Cell biology, Gene Expression Regulation, Neoplastic, 030104 developmental biology, 570 Life sciences, biology, Signal transduction, Carrier Proteins, Lysosomes, 030217 neurology & neurosurgery, Protein Binding, Signal Transduction |
| الوصف: | 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. During autophagy, AMPK and mTOR associate with ULK1 and regulate phosphatidylinositol 3-phosphate (PtdIns3P) production that mediates autophagosome formation via WIPI proteins. Here the authors show WIPI3 and WIPI4 have a scaffolding function upstream of PtdIns3P production and have a role in the PtdIns3P effector function of WIPI1-WIPI2 at nascent autophagosomes. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d0fdde3b8d0a338e60027cb70446bd37Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d0fdde3b8d0a338e60027cb70446bd37 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |