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mTOR-dependent phosphorylation controls TFEB nuclear export

Author

Listed:
  • Gennaro Napolitano

    (Telethon Institute of Genetics and Medicine (TIGEM)
    Federico II University)

  • Alessandra Esposito

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • Heejun Choi

    (Howard Hughes Medical Institute)

  • Maria Matarese

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • Valerio Benedetti

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • Chiara Di Malta

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • Jlenia Monfregola

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • Diego Luis Medina

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • Jennifer Lippincott-Schwartz

    (Howard Hughes Medical Institute
    National Institutes of Health)

  • Andrea Ballabio

    (Telethon Institute of Genetics and Medicine (TIGEM)
    Federico II University
    Baylor College of Medicine)

Abstract

During starvation the transcriptional activation of catabolic processes is induced by the nuclear translocation and consequent activation of transcription factor EB (TFEB), a master modulator of autophagy and lysosomal biogenesis. However, how TFEB is inactivated upon nutrient refeeding is currently unknown. Here we show that TFEB subcellular localization is dynamically controlled by its continuous shuttling between the cytosol and the nucleus, with the nuclear export representing a limiting step. TFEB nuclear export is mediated by CRM1 and is modulated by nutrient availability via mTOR-dependent hierarchical multisite phosphorylation of serines S142 and S138, which are localized in proximity of a nuclear export signal (NES). Our data on TFEB nucleo-cytoplasmic shuttling suggest an unpredicted role of mTOR in nuclear export.

Suggested Citation

  • Gennaro Napolitano & Alessandra Esposito & Heejun Choi & Maria Matarese & Valerio Benedetti & Chiara Di Malta & Jlenia Monfregola & Diego Luis Medina & Jennifer Lippincott-Schwartz & Andrea Ballabio, 2018. "mTOR-dependent phosphorylation controls TFEB nuclear export," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05862-6
    DOI: 10.1038/s41467-018-05862-6
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    Cited by:

    1. Logan Brase & Shih-Feng You & Ricardo D’Oliveira Albanus & Jorge L. Del-Aguila & Yaoyi Dai & Brenna C. Novotny & Carolina Soriano-Tarraga & Taitea Dykstra & Maria Victoria Fernandez & John P. Budde & , 2023. "Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Marie Villares & Nelly Lourenço & Ivan Ktorza & Jérémy Berthelet & Aristeidis Panagiotou & Aurélie Richard & Angélique Amo & Yulianna Koziy & Souhila Medjkane & Sergio Valente & Rossella Fioravanti & , 2024. "Theileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Flavia Giamogante & Lucia Barazzuol & Francesca Maiorca & Elena Poggio & Alessandra Esposito & Anna Masato & Gennaro Napolitano & Alessio Vagnoni & Tito Calì & Marisa Brini, 2024. "A SPLICS reporter reveals $${{{{{\boldsymbol{\alpha }}}}}}$$ α -synuclein regulation of lysosome-mitochondria contacts which affects TFEB nuclear translocation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Dengqin Zhong & Ruiyun Wang & Hongjing Zhang & Mengmeng Wang & Xuxia Zhang & Honghong Chen, 2023. "Induction of lysosomal exocytosis and biogenesis via TRPML1 activation for the treatment of uranium-induced nephrotoxicity," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Kaushal Asrani & Juhyung Woo & Adrianna A. Mendes & Ethan Schaffer & Thiago Vidotto & Clarence Rachel Villanueva & Kewen Feng & Lia Oliveira & Sanjana Murali & Hans B. Liu & Daniela C. Salles & Brando, 2022. "An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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