Autophagy, the Ubiquitin proteasome system, and the MAPK pathway control the temperature dependence of synaptic growth

There is clear evidence that Earth’s temperature is rising at an unprecedented rate. While consequences on ecosystems are being extensively studied, little is known about the consequences of temperature on the nervous system of ectothermic animals. Here we used the Drosophila model NMJ to assess the effect of temperature on the synaptic growth of a phasic, and a tonic, motoneuron. We find that the tonic neuron’s synaptic size is not affected by temperature, however we do observe a temperature-dependent synaptic growth in the phasic neuron, which might be related to the increased motility observed previously at higher temperatures. We find that the level of autophagy activity changes with temperature and that autophagy genes are responsible for the temperature dependence of synaptic growth. We present evidence that this regulation could occur through the major synaptic growth regulator and ubiquitin ligase Highwire, and a pathway involving the Mitogen-Activated Protein Kinases. We present a new function for the MAPKKK, Wallenda and the MAPK P38b in directing the additional synaptic growth that takes place between 25°C and 29°C. This illustrates that temperature has different effects on a diverse population of neurons and that distinct genetic pathways are involved in regulating temperature driven changes.