Protein Degradation Pathways Regulate Neurite Pruning in Drosophila

来源 :2015亚太发育生物学国际研讨会 | 被引量 : 0次 | 上传用户:yongren803
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  Selective removal of unnecessary or exuberant neuronal processes without loss of parent neurons, referred to as neurite pruning, is crucial for the maturation of the nervous system during animal development.In Drosophila, dendritic arborization ddaC sensory neurons selectively prune their larval dendrites in response to a late-larval pulse of the molting steroid hormone ecdysone.Developmental dendrite pruning shares a number of features with pathological neurite degeneration occuring in age-dependent neurological disorders and therefore also serves as an excellent model for understanding molecular and cellular mechanisms of neurodegeneration.We previously conducted two large-scale genetic screens and identified a pathway composed of the transcription factor Sox14 and the important cytoskeletal regulator Mical that act downstream of the ecdysone signaling to regulate neurite pruning (Kirilly D., et al., Nat Neurosci.2009).Moreover, we also identified a Brahma (Brm)-containing chromatin remodeler, a histone acetyltransferase CREB-binding protein (CBP) (Kirilly D.et al., Neuron 2011), a conserved SCF E3 ligase that inactivates the insulin signaling pathway during dendrite pruning (Wong JJL.et al.,PLoS Biol.2013).We have recently identified Rab5/ESCRT-dependent endocytic pathways which play crucial roles in dendrite pruning of ddaC sensory neurons during early metamorphosis.We further identified a highly conserved L1-type cell adhesion molecule (CAM) Neuroglian (Nrg) that is accumulated in Rab5 or ESCRT mutant ddaC neurons.This study demonstrates the first cell adhesion molecule that instructs dendrite pruning and defines an important mechanism whereby sensory neurons, via endolysosomal pathway, downregulate the cell-surface molecule to trigger dendrite pruning.Finally, I will also summarize the progress of the recent projects in dendrite pruning.
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