[bioRxiv] Systemic Activation Coordinates The Heat Shock Response Of The Insulin/IGF-1 Pathway In Ca
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 homeostasis (1). The insulin/IGF1 signaling (IIS) pathway, which has diverse roles from metabolism to stress response and longevity, is activated as part of the HSR (2,3,4). Recent evidence suggest that the IIS pathway is able to affect proteostasis non autonomously (5,6), 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 DAF16 functions as the major target of the IIS pathway (7) and, together with the heat-shock factor HSF1, induce the expression of small heat shock proteins in response to heat shock (3,8,9,10). Here we use a novel microfluidic device that allows precise control of the spatiotemporal temperature profile to show that cellular activation of DAF16 integrates local temperature sensation with systemic signals. We demonstrate that DAF16 activation in head sensory neurons is essential for DAF16 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.
Ronen Binyamin Kopito, Kathie Watkins, Erel Levine