MECHANISTIC STUDY ON THE ROLE OF KINESIN-3 IMAC AND ADAPTOR PROTEINS IN REGULATING DENDRITE PRUNING IN DROSOPHILA MELANOGASTER

Abstract

Pruning, referred to as selective removal of unnecessary neurites without cell death, occurs in both vertebrates and invertebrates. The Drosophila dorsal class IV dendritic arborization neuron (ddaC) can serve as an excellent model to study the mechanisms of dendrite pruning. To identify novel molecules orchestrating this developmental degeneration process, I performed an RNAi screen, from which a previously uncharacterized gene named pruning defect 1(prd1) was isolated. It binds to Adaptor Protein (AP)-2 complex and regulates dendrite pruning in a cell-autonomous manner. Consistently, AP-2 complex dependent endocytic degradation pathway is also important for dendrite pruning. Interestingly, Prd1 also complexes with a Kinesin-3 family member Immaculate connections (Imac), which plays a critical role in regulating dendrite pruning as well. With the help of Prd1, Imac transports AP-2 enriched Clathrin Coated Vesicles (CCVs) or endocytic vesicles from plasma membrane to early endosomes along microtubule plus end. Moreover, loss function of imac results in aggregation of Prd1, AP-2 and CCVs/endocytic vesicles on aberrant, enlarged endosomes. Therefore, Imac may facilitate dendrite pruning by regulating distribution of CCVs/endocytic vesicles in sensory neurons of Drosophila.