Intertissue crosstalk: Regulation of organismal proteostasis by transcellular chaperone signaling

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• Dr Patricija van Oosten-Hawle, Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA
• Monday 13 January 2014, 16:15-17:15
• Max Perutz Lecture Theatre, MRC Laboratory of Molecular Biology.

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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. Equally, tissue-specific induction of the HSR leads to systemic propagation of the response in a pha-4 dependent manner. Thus, this transcellular chaperone signaling response ensures that a local imbalance of proteostasis within any tissue at risk is responded by a compensatory activation of a stress response in adjacent tissues that confers a systemic protective response. To understand how a stress event in the sender tissue initiates a protective response in target tissues and to identify the transcellular stress signal, we analyzed organism-wide transcriptional changes upon a tissue-specific imbalance of chaperone expression, using RNA -seq. We are currently investigating a set of candidate genes, regulated downstream of PHA -4 and predicted to localize extracellularly, for their involvement in transcellular chaperone signaling.

This talk is part of the Cambridge Neuroscience Seminars series.

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