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SUMMARY:Intertissue crosstalk: Regulation of organismal proteostasis by tr
 anscellular chaperone signaling - Dr Patricija van Oosten-Hawle\, Departme
 nt of Molecular Biosciences\, Northwestern University\, Evanston\, IL\, US
 A
DTSTART:20140113T161500Z
DTEND:20140113T171500Z
UID:TALK50052@talks.cam.ac.uk
CONTACT:24218
DESCRIPTION:A major challenge for metazoans is to ensure that different ti
 ssues expressing distinctive proteomes are\, nevertheless\, well protected
  at an organismal level from proteotoxic stress.  We have examined this an
 d 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 enhan
 ced expression of HSP90 in muscle cells\, but equally by elevated expressi
 on of HSP90 in intestine or neuronal cells. Equally\, tissue-specific indu
 ction of the HSR leads to systemic propagation of the response in a pha-4 
 dependent manner. Thus\, this transcellular chaperone signaling response e
 nsures that a local imbalance of proteostasis within any tissue at risk is
  responded by a compensatory activation of a stress response in adjacent t
 issues that confers a systemic protective response. To understand how a st
 ress event in the sender tissue initiates a protective response in target 
 tissues and to identify the transcellular stress signal\, we analyzed orga
 nism-wide transcriptional changes upon a tissue-specific imbalance of chap
 erone 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 signali
 ng.
LOCATION:Max Perutz Lecture Theatre\, MRC Laboratory of Molecular Biology
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