In the nematode Caenorhabditis elegans, the heat shock response (HSR) is regulated at the organismal level by a network of thermosensory neurons that senses elevated temperatures and activates the HSR in remote tissues. Which neuronal receptors are required for this signaling mechanism and in which neurons they function are largely unanswered questions. Here we used worms that were engineered to exhibit RNA interference hypersensitivity in neurons to screen for neuronal receptors that are required for the activation of the HSR and identified a putative G-protein coupled receptor (GPCR) as a novel key component of this mechanism. This gene, which we termed GPCR thermal receptor 1 (gtr-1), is expressed in chemosensory neurons and has no role in heat sensing but is critically required for the induction of genes that encode heat shock proteins in non-neural tissues upon exposure to heat. Surprisingly, the knock-down of gtr-1 by RNA interference protected worms expressing the Alzheimer's-disease-linked aggregative peptide Aβ3-42 from proteotoxicity but had no effect on lifespan. This study provides several novel insights: (1) it shows that chemosensory neurons play important roles in the nematode's HSR-regulating mechanism, (2) it shows that lifespan and heat stress resistance are separable, and (3) it strengthens the emerging notion that the ability to respond to heat comes at the expense of protein homeostasis (proteostasis).