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mTORC1 controls Golgi architecture and vesicle secretion by phosphorylation of SCYL1

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  • Stéphanie Kaeser-Pebernard, University of Fribourg
  • ,
  • Christine Vionnet, University of Fribourg
  • ,
  • Muriel Mari
  • Devanarayanan Siva Sankar, University of Fribourg
  • ,
  • Zehan Hu, University of Fribourg
  • ,
  • Carole Roubaty, University of Fribourg
  • ,
  • Esther Martínez-Martínez, University of Fribourg
  • ,
  • Huiyuan Zhao, University of Fribourg
  • ,
  • Miguel Spuch-Calvar, University of Fribourg
  • ,
  • Alke Petri-Fink, University of Fribourg
  • ,
  • Gregor Rainer, University of Fribourg
  • ,
  • Florian Steinberg, University of Freiburg
  • ,
  • Fulvio Reggiori
  • Jörn Dengjel, University of Fribourg

The protein kinase mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and proliferation, supporting anabolic reactions and inhibiting catabolic pathways like autophagy. Its hyperactivation is a frequent event in cancer promoting tumor cell proliferation. Several intracellular membrane-associated mTORC1 pools have been identified, linking its function to distinct subcellular localizations. Here, we characterize the N-terminal kinase-like protein SCYL1 as a Golgi-localized target through which mTORC1 controls organelle distribution and extracellular vesicle secretion in breast cancer cells. Under growth conditions, SCYL1 is phosphorylated by mTORC1 on Ser754, supporting Golgi localization. Upon mTORC1 inhibition, Ser754 dephosphorylation leads to SCYL1 displacement to endosomes. Peripheral, dephosphorylated SCYL1 causes Golgi enlargement, redistribution of early and late endosomes and increased extracellular vesicle release. Thus, the mTORC1-controlled phosphorylation status of SCYL1 is an important determinant regulating subcellular distribution and function of endolysosomal compartments. It may also explain the pathophysiology underlying human genetic diseases such as CALFAN syndrome, which is caused by loss-of-function of SCYL1.

Original languageEnglish
Article number4685
JournalNature Communications
Volume13
Issue1
Number of pages21
ISSN2041-1723
DOIs
Publication statusPublished - Aug 2022

    Research areas

  • AUTOPHAGY, BREAST-CANCER, COATOMER, LIVER-FAILURE, MUTATIONS, PATHWAYS, PROTEOME, RAG GTPASES, RAPAMYCIN, TORC1

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