Glucosylation by the Legionella Effector SetA Promotes the Nuclear Localization of the Transcription Factor TFEB
Wendy H.J. Beck,
Dongsung Kim,
Jishnu Das,
Haiyuan Yu,
Marcus B. Smolka,
Yuxin Mao
Affiliations
Wendy H.J. Beck
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
Dongsung Kim
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
Jishnu Das
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Computational Biology, Cornell University, Ithaca, NY 14853, USA
Haiyuan Yu
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Computational Biology, Cornell University, Ithaca, NY 14853, USA
Marcus B. Smolka
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
Yuxin Mao
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Corresponding author
Summary: 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.
