PT  - JOURNAL ARTICLE
AU  - Ronen B Kopito
AU  - Kathie Watkins
AU  - Erel Levine
TI  - Systemic activation coordinates the heat shock response of the insulin/IGF-1 pathway in <em>Caenorhabditis elegans</em>
AID  - 10.1101/131375
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 131375
4099  - http://biorxiv.org/content/early/2017/05/06/131375.short
4100  - http://biorxiv.org/content/early/2017/05/06/131375.full
AB  - Exposure to high temperatures has an adverse effect on cellular processes and results in activation of the cellular heat shock response (HSR), a highly conserved program of inducible genes to maintain protein homeostasis1. The insulin/IGF-1 signaling (IIS) pathway, which has diverse roles from metabolism to stress response and longevity, is activated as part of the HSR2–4. Recent evidence suggest that the IIS pathway is able to affect proteostasis non-autonomously5,6, yet it is not known if it is activated autonomously in stressed cells or systemically as part of an organismic program. In Caenorhabditis elegans, the single forkhead box O (FOXO) homologue DAF-16 functions as the major target of the IIS pathway7 and, together with the heat-shock factor HSF-1, induce the expression of small heat shock proteins in response to heat shock8–10,3. Here we use a novel microfluidic device that allows precise control of the spatiotemporal temperature profile to show that cellular activation of DAF-16 integrates local temperature sensation with systemic signals. We demonstrate that DAF-16 activation in head sensory neurons is essential for DAF-16 activation in other tissues, but show that no known thermosensory neuron is individually required. Our findings demonstrate that systemic and cell-autonomous aspects of stress response act together to facilitate a coordinated cellular response at the organismic level.