Temperature is one of the most pervasive factors that affect biological systems. Thus, it is not surprising that almost all organisms have evolved mechanisms to sense and respond to changes in environmental temperature. Indeed, the ability to seek out optimal temperatures for growth and reproduction is a common trait among ectothermic organisms. For most biological processes there is a narrow range of optimal temperatures outside of which efficiency steeply declines. Temperatures only a few degrees outside the normal range for a species may lead to direct damage of cellular machinery. Almost all cells possess the intrinsic ability to elicit a heat shock response (HSR) to protect their proteins and other macromolecules from heat stress. This response includes the production of a highly conserved group of molecular chaperones called the heat shock proteins. However, the mechanisms that regulate and integrate a cellular HSR into a HSR at the tissue and organismal level have received little attention. Veena Prahlad and colleagues at Northwestern University set out to investigate the role of temperature sensing by thermosensory AFD neurons in regulating the cellular HSR in the nematode worm C. elegans.
To investigate the role of the AFD neurons in the cellular HSR, they raised wild-type and mutant worms that lacked functional AFD neurons at 20°C and then exposed them to a transient heat shock of 30 or 34°C for 15 min. After allowing the worms to recover for 2 h, they measured the total amount of mRNA for a major heat shock protein (cytoplasmic hsp70) in the whole worms. They also investigated the location of hsp70 expression within a worm using a green fluorescent protein reporter.
The team found that mutant worms lacking functional AFD neurons had significantly reduced levels of hsp70 mRNA compared with the wild-type worms following the heat shock regimen. All mutant worms' cells produced less hsp70 mRNA in the absence of AFD thermosensing, despite retaining the HSR cellular machinery. The attenuated HSR in these worms also led to a lower tolerance of heat stress. Further, the team illustrated that this affect was temperature specific by eliciting a full-scale HSR in mutant worms that lacked functional AFD neurons by exposing them to the heavy metal cadmium, which is known to induce a HSR in the cells of a variety of organisms.
Prahlad and the team also explored whether the worm's metabolic state influences the HSR by repeating their experiments in either the presence or the absence of dauer hormone. High amounts of dauer hormone are produced when population densities are high and food becomes limited. The hormone signals larvae to enter a state of metabolic dormancy to await more favourable conditions. When exposed to heat shock in the presence of dauer hormone, the wild-type worms responded with an attenuated HSR. However, the worms that lacked functional AFD neurons produced a HSR that exceeded that of control wild-type worms. Based on this unexpected result, the team suggest that information on the nematode's metabolic state is integral to the regulation of the organismal HSR, and that thermal and metabolic inputs are responsible for mutually down regulating the HSR.
Prahlad and colleagues have illustrated that the cellular HSR is not regulated within each cell of C. elegans in response to temperature stress, but is instead regulated by the thermosensory AFD neurons. Their results are consistent with a model that integrates metabolic and thermosensory signals to generate an organismal-level HSR. The authors suggest that the AFD neurons must be communicating with individual cells in the nematode's body via an unidentified extracellular signalling molecule because these neurons do not directly innervate the cells that respond to heat stress with a HSR.
