THE ROLE OF SECRETORY PATHWAY IN REGULATING NEURONAL PRUNING IN DROSOPHILA

Abstract

Neurites, e.g. axon, dendrite and synapse, are important for neuronal activity and formation of proper neuronal circuits. Neuronal pruning is the selective removal of excessive neurites, without causing cell death. It is crucial for the formation of adult nervous system, and defective pruning can lead to autism and other neuronal disorders. It has been implicated that the Golgi based secretory pathway regulates neuronal pruning. However, the mechanistic details remain unclear. In Drosophila, dendritic arborization neurons, ddaCs, selectively prune their larval dendrites during metamorphosis. From a RNAi screen, I isolated Arf1 GTPase and Sec71 as novel regulators for dendrite pruning. Through a series of assays, I demonstrated Sec71 is an Arf1 Guanine nucleotide exchange factor (GEF) in Drosophila. Moreover, Sec71 and Arf1 are colocalized at trans-Golgi in sensory neurons, and act cooperatively to control dendrite pruning. Loss of Sec71/Arf1 function leads to similar failure of the L1-type cell adhesion molecule (CAM) Neuroglian (Nrg) downregulation prior to pruning in ddaC neurons. Epistasis experiments indicate that Sec71/Arf1-mediated secretory pathway regulates Rab5-mediated endocytic pathway to restrain the inhibitory role of Nrg during dendrite pruning. Thus, this study defines an important mechanism that Sec71/Arf1-mediated secretory pathway facilitates sensory neuron dendrite pruning via downregulation of an important CAM.