CIBSS - Centre for integrative Biological Signalling StudiesCIBSS

Associate Investigators

Prof. Dr. Sabine Rospert

Contact

Prof. Dr. Sabine Rospert
Institute of Biochemistry and Molecular Biology (Faculty of Medicine)
University of Freiburg

T +49 761 203 5259
sabine.rospert(at)biochemie.uni-freiburg.de

Further Information

First, we study how glucose availability determines the metabolic switch between fermentation and respiration in yeast. When glucose is available, respiration is turned off by a mechanism termed glucose repression. Release from glucose repression depends on the highly conserved metabolic kinase SNF1, which is the homolog of mammalian AMPK. SNF1 activity is regulated by the essential PP1-type protein phosphatase Glc7 and its regulatory subunit Reg1. We have characterized a crosstalk between the cytosolic chaperone Ssb, the 14-3-3 protein Bmh, and the Glc7/Reg1 phosphatase, which fine tunes SNF1 activity.

Second, we investigate various facets of the early steps of protein biogenesis, in which ribosomes, beyond their role in protein synthesis, serve as a hub for downstream processes. As an example, targeting of newly synthesized membrane proteins requires a regulated crosstalk between ribosomes, cytosolic targeting factors, and membrane receptors. The major challenge during membrane protein biogenesis is how to prevent aggregation prior to membrane integration. In the case of ER membrane proteins, this is achieved by highly specific machineries, which mediate co-translational membrane integration. In contrast, mitochondrial membrane proteins reach their destination mainly post-translationally and all-purpose cytosolic chaperones, such as Hsp70 and Hsp90, are thought to shield transmembrane domains during passage through the cytosol. The exact targeting routes of mitochondrial membrane proteins, however, are only poorly understood.

 

Keywords

Ribosomes, translation, co-translational protein folding, co-translational targeting to the ER, chaperones, ribosome-bound protein biogenesis factors, signaling kinases, regulation of glucose metabolism, AMPK/SNF1, TORC1

10 selected publications:

  • Ribosome-bound Get4/5 facilitates the capture of tail-anchored proteins by Sgt2 in yeast.
    Zhang Y, De Laurentiis E, Bohnsack KE, Wahlig M, Ranjan N, Gruseck S, Hackert P, Wölfle T, Rodnina MV, Schwappach B, Rospert S (2021)
    Nat Commun 12: 782
  • The ribosome-associated complex RAC serves in a relay that directs nascent chains to Ssb.
    Zhang Y, Valentin Gese G, Conz C, Lapouge K, Kopp J, Wölfle T, Rospert S*, Sinning I* (2020)
    Nat Commun 11: 1504  *co-corresponding
  • A dual role of the ribosome-bound chaperones RAC/Ssb in maintaining the fidelity of translation termination.
    Gribling-Burrer AS, Chiabudini M, Zhang Y, Qiu Z, Scazzari M, Wölfle T, Wohlwend D, Rospert S (2019)
    Nucleic Acids Res: 7018-7034
  • Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation.
    Puleston DJ, Buck MD, Klein Geltink RI, Kyle RL, Caputa G, O'Sullivan D, Cameron AM, Castoldi A, Musa Y, Kabat AM, Zhang Y, Flachsmann LJ, Field CS, Patterson AE, Scherer S, Alfei F, Baixauli F, Austin SK, Kelly B, Matsushita M, Curtis JD, Grzes KM, Villa M, Corrado M, Sanin DE, Qiu J, Pallman N, Paz K, Maccari ME, Blazar BR, Mittler G, Buescher JM, Zehn D, Rospert S, Pearce EJ, Balabanov S, Pearce EL (2019)
    Cell Metab 30: 352-363 e358
  • The yeast Hsp70 homolog Ssb: a chaperone for general de novo protein folding and a nanny for specific intrinsically disordered protein domains.
    Hübscher V, Mudholkar K, Rospert S (2017)
    Curr Genet 63: 9-13
  • The Hsp70 homolog Ssb affects ribosome biogenesis via the TORC1-Sch9 signaling pathway.
    Mudholkar K, Fitzke E, Prinz C, Mayer MP, Rospert S (2017)
    Nat Commun 8: 1-14
  • Two chaperones locked in an embrace: Structure and function of the ribosome-associated complex RAC.
    Zhang Y, Sinning I, Rospert S (2017)
    Nat Struct Mol Biol 24: 611-619
  • Interaction of the cotranslational Hsp70 Ssb with ribosomal proteins and rRNA depends on its lid domain.
    Gumiero A, Conz C, Gesé GV, Zhang Y, Weyer FA, Lapouge K, Kappes J, von Plehwe U, Schermann G, Fitzke E, Wölfle T, Fischer T, Rospert S*, Sinning I* (2016)
    Nat Commun 7: 1-12
    *co-corresponding
  • The Hsp70 homolog Ssb and the 14-3-3 protein Bmh1 jointly regulate transcription of glucose repressed genes in Saccharomyces cerevisiae.
    Hübscher V, Mudholkar K, Chiabudini M, Fitzke E, Wölfle T, Pfeifer D, Drepper F, Warscheid B, Rospert S (2016)
    Nucleic Acids Res 44: 5629-5645
  • Cotranslational intersection between the SRP and GET targeting pathways to the ER of Saccharomyces cerevisiae.
    Zhang Y, Schaffer T, Wölfle T, Fitzke E, Thiel G, Rospert S (2016)
    Mol Cell Biol 36: 2374-2383