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Seminar

Monday, June 11th, 2018
From 11h30 To 12h30
Centre de Recherche - Orsay - Amphithéâtre du Bâtiment 111

Le Bateau Ivre de la Cellule: The origin and growth of the phagophore of autophagy

Autophagy is a conserved mechanism that is essential for cell survival in starvation and for cellular homeostasis. The autophagosome and the proteasome comprise the two main pathways for the degradation of proteins. Autophagy proceeds by the engulfment of bulk cytosol and organelles by a cup- (or boat-, hence the "Bateau" of the title) shaped double membrane sheet known as the phagophore, which matures into the autophagosome. Two protein complexes control the initiation of the phagophore: the Atg1/ULK1 kinase complex and the class III phosphatidylinositol 3-kinase (PI3KC3).  ULK1 is in turn regulated downstream of the lysosomal protein kinase complex mTORC1 and its activator, the Ragulator-RagA/B-RagC/C complex. Our laboratory has been applying crystallography, electron microscopy, mass spectrometry, and allied biophysical techniques, in conjunction with cell biology approaches, to understand how these complexes are organized in three-dimensional space and time, and how their architectures underpin their regulation and activity. This has led to insights both into the shaping and scaffolding of the phagophore, and to the switching on and off of its growth.

Speaker(s)

Prof. Jim Hurley
Professor

California Institute for Quantitative Biosciences, University of California, Berkeley

Invited by

Patricia Bassereau
Domain 4 - UMR 168 - Physical chemistry

Institut Curie

Bruno Goud
Domain 4 - UMR 168 - Physical chemistry

Institut Curie

Contact

Prof. Jim Hurley

Professor

California Institute for Quantitative Biosciences, University of California, Berkeley

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Patricia Bassereau

Institut Curie

Send an e-mail

Bruno Goud

Institut Curie

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Learn more

Recent papers:

- Gardner B. M., Castanzo D. T., Chowdhury S., Stjepanovic G., Stefely M. S., Hurley J. H., Lander G. C., Martin A. The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading Nat. Commun. 9 135 (2018)
- Schoneberg J., Lee I. H., Iwasa J. H., Hurley J. H. Reverse-topology membrane scission by the ESCRT proteins Nat. Rev. Mol. Cell Biol. 18 5-17 (2017)
- Young L. N., Cho K., Lawrence R., Zoncu R., Hurley J. H. Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy Proc Natl Acad Sci U S A 113 8224-8229 (2016)
- Schulze-Gahmen U., Echeverria I., Stjepanovic G., Bai Y., Lu H., Schneidman-Duhovny D., Doudna J. A., Zhou Q., Sali A., Hurley J. H. Insights into HIV-1 proviral transcription from integrative structure and dynamics of the Tat:AFF4:P-TEFb:TAR complex Elife 5 (2016)
- Carlson L. A., Bai Y., Keane S. C., Doudna J. A., Hurley J. H. Reconstitution of selective HIV-1 RNA packaging in vitro by membrane-bound Gag assemblies Elife 5 (2016)
- Lee I. H., Kai H., Carlson L. A., Groves J. T., Hurley J. H. Negative membrane curvature catalyzes nucleation of endosomal sorting complex required for transport (ESCRT)-III assembly Proc Natl Acad Sci U S A 112 15892-15897 (2015)