Fig. 8: Sensory temperature perception and proteostasis regulation.

a In WT worms, external stimuli, such as warm temperature, are perceived and processed normally via sensory neurons such as AWA (and possibly other sensory neurons, including ASH), reducing AFD signalling (sensation ‘warm’). The red lines schematically show the length of all cilia, which are longer in WT, whereas the distal segments are absent in the dyf-1(mn335) mutant. UPS function in the intestine does not primarily depend on INS-5 or calcineurin signalling. Thus, WT worms increase their protein degradation in response to warm temperature (dotted line in the graph), resulting in decreased amounts of proteasomal substrates (substrate amt. dark line) at higher temperature (substrate amt. dark line). dyf-1(-) mutant worms exhibit defects in distal cilia formation and are unable to properly sense ambient temperature (no sensation) due to decreased AWA function creating a neuronal signal that involves the aberrant function of the AFD neurons which fail to sense the ambient temperature correctly (indicated by black arrow). This signal includes DCV secretion and the neuropeptide FLP-3 that blocks the UPS in the intestine. The induced AFD signal increases INS-5 to reduce UPS function. In parallel, tax-6 loss-of-function is tipping the balance towards the action of DAF-16 to control the UPS. Hence, dyf-1(-) worms fail to adjust their protein degradation rate (dotted grey line in the graph) due to loss of temperature sensation and accumulate proteasomal substrates (dark line in the graph).