Glucosylation by the Legionella Effector SetA Promotes the Nuclear Localization of the Transcription Factor TFEB

• Published in: iScience 2020-07, Vol.23 (7), p.101300-101300, Article 101300
• Main Authors: Beck, Wendy H.J., Kim, Dongsung, Das, Jishnu, Yu, Haiyuan, Smolka, Marcus B., Mao, Yuxin
• Format: Article
• Language: English
• Subjects: Microbiology; Molecular Biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.101300

Legionella pneumophila is an intracellular pathogen that requires nutrients from the host for its replication. It has been shown that replicating L. pneumophila prefers amino acids as main sources of carbon and energy. The homeostasis of amino acids in eukaryotic cells is regulated by the transcription factor EB (TFEB), which translocates into the nucleus and activates genes for autophagy and lysosomal biogenesis. Here we show that the Legionella effector SetA causes a robust nuclear translocation of TFEB when exogenously expressed in mammalian cells and that the translocation is dependent on the glucosyltransferase activity of SetA. We further show that SetA directly glucosylates TFEB at multiple sites. Our findings of TFEB glucosylation by SetA may suggest an alternative strategy for exploiting host nutrients in addition to the control of host mTORC1 signaling by L. pneumophila. Our results provide further insight into the molecular mechanism of the delicate TFEB nuclear shuttling. [Display omitted] •The Legionella effector SetA causes robust nuclear enrichment of TFEB•SetA directly glucosylates TFEB at multiple Ser/Thr sites•Glucosylation of the S138 site by SetA prevents TFEB nuclear export•Glucosylation near the S211 site of TFEB disrupts the binding between TFEB and 14-3-3 Molecular Biology; Microbiology