title: Endocytic pathways downregulate the L1-type cell adhesion molecule neuroglian to promote dendrite pruning in Drosophila.
abstract: Pruning of unnecessary axons and/or dendrites is crucial for maturation of the nervous system. However, little is known about cell adhesion molecules (CAMs) that control neuronal pruning. In Drosophila, dendritic arborization neurons, ddaCs, selectively prune their larval dendrites. Here, we report that Rab5/ESCRT-mediated endocytic pathways are critical for dendrite pruning. Loss of Rab5 or ESCRT function leads to robust accumulation of the L1-type CAM Neuroglian (Nrg) on enlarged endosomes in ddaC neurons. Nrg is localized on endosomes in wild-type ddaC neurons and downregulated prior to dendrite pruning. Overexpression of Nrg alone is sufficient to inhibit dendrite pruning, whereas removal of Nrg causes precocious dendrite pruning. Epistasis experiments indicate that Rab5 and ESCRT restrain the inhibitory role of Nrg during dendrite pruning. Thus, this study demonstrates the cell-surface molecule that controls dendrite pruning and defines an important mechanism whereby sensory neurons, via endolysosomal pathway, downregulate the cell-surface molecule to trigger dendrite pruning.
authors.affiliation: Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, Singapore.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, Singapore; NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences, Singapore 117456, Singapore.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, Singapore; NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences, Singapore 117456, Singapore.
authors.forename: Jack Jing Lin
authors.initials: JJ
authors.lastname: Wong
authors.affiliation: Neuroscience and Behavioural Disorders Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore; National Neuroscience Institute, Singapore 308433, Singapore; Department of Physiology, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Kah-Leong
authors.initials: KL
authors.lastname: Lim
authors.affiliation: Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, Singapore.
authors.forename: Yih-Cherng
authors.initials: YC
authors.lastname: Liou
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences, Singapore 117456, Singapore; Neuroscience and Behavioural Disorders Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore; Department of Physiology, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 1 Research Link, Singapore 117604, Singapore; NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences, Singapore 117456, Singapore; Neuroscience and Behavioural Disorders Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore. Electronic address: fengwei@tll.org.sg.
authors.forename: Fengwei
authors.initials: F
authors.lastname: Yu
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D015536:Down-Regulation; D004330:Drosophila / Q000196:embryology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D004843:Epistasis, Genetic; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C061745:Nrg protein, Drosophila; C586289:Rab5 protein, Drosophila; D020696:rab5 GTP-Binding Proteins