van Oosten-Hawle

Institute:Dep. Mol. Biosciences, Rice Inst. Biomedical Research, Northwestern University, Evanston, USA
Title:Intertissue crosstalk: Transcellular chaperone signaling regulates organismal proteostasis in C. elegans
Abstract:["A major challenge for metazoans is to ensure that different tissues expressing distinctive proteomes are, nevertheless, well protected at an organismal level from proteotoxic stress. We have examined this and show that expression of endogenous metastable protein sensors in muscle cells induces a systemic stress response throughout multiple tissues of C. elegans. Suppression of misfolding in muscle cells was achieved by enhanced expression of HSP90 in muscle cells, but equally by elevated expression of HSP90 in intestine or neuronal cells. This cell-non-autonomous control of HSP90 expression relies upon transcriptional feedback between somatic tissues mediated by the FoxA transcription factor PHA-4. Importantly, this trans-cellular chaperone signaling response to a perturbed proteostasis network is also observed in mammalian tissue cells. These results provide the framework for a novel evolutionary conserved mechanism that balances tissue requirements with the maintenance of organismal proteostasis."]
Host:Ineke Braakman