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

Abstract 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 larval NMJ to ask whether phasic 1s and tonic 1b motor neuron terminals differ in their structural response to rearing temperature. We find that the tonic 1b terminal's bouton number 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 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.