title: ADP-ribosylation factor 6 (ARF6) bidirectionally regulates dendritic spine formation depending on neuronal maturation and activity.
abstract: Recent studies have reported conflicting results regarding the role of ARF6 in dendritic spine development, but no clear answer for the controversy has been suggested. We found that ADP-ribosylation factor 6 (ARF6) either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation increased the spine formation in developing neurons, whereas it decreased spine density in mature neurons. Genome-wide microarray analysis revealed that ARF6 activation in each stage leads to opposite patterns of expression of a subset of genes that are involved in neuronal morphology. ARF6-mediated Rac1 activation via the phospholipase D pathway is the coincident factor in both stages, but the antagonistic RhoA pathway becomes involved in the mature stage. Furthermore, blocking neuronal activity in developing neurons using tetrodotoxin or enhancing the activity in mature neurons using picrotoxin or chemical long term potentiation reversed the effect of ARF6 on each stage. Thus, activity-dependent dynamic changes in ARF6-mediated spine structures may play a role in structural plasticity of mature neurons.
authors.affiliation: From the Department of Physiology and Biomedical Sciences, Neuroscience Research Institute, Medical Research Center, Biomembrane Plasticity Research Center, and.
authors.forename: Yoonju
authors.initials: Y
authors.lastname: Kim
authors.affiliation: From the Department of Physiology and Biomedical Sciences, Biomembrane Plasticity Research Center, and.
authors.forename: Sang-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: From the Department of Physiology and Biomedical Sciences, Neuroscience Research Institute, Medical Research Center, Biomembrane Plasticity Research Center, and.
authors.forename: Joohyun
authors.initials: J
authors.lastname: Park
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering and Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, Kyungbook 790-784, South Korea, and.
authors.forename: Minhyung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Interdisciplinary Program in Neuroscience, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Boyoon
authors.initials: B
authors.lastname: Lee
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering and Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, Kyungbook 790-784, South Korea, and Center for Systems Biology of Plant Senescence and Life History, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 711-873, South Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: From the Department of Physiology and Biomedical Sciences, Neuroscience Research Institute, Medical Research Center, Biomembrane Plasticity Research Center, and Interdisciplinary Program in Neuroscience, Seoul National University College of Medicine, Seoul 110-799, South Korea, sunghoe@snu.ac.kr.
authors.forename: Sunghoe
authors.initials: S
authors.lastname: Chang
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D049229:Dendritic Spines; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D009474:Neurons / Q000166:cytology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000089982:ADP-Ribosylation Factor 6; D034741:RNA, Small Interfering; D020727:ADP-Ribosylation Factors; C000715349:Arf6 protein, rat
keywords: ADP-ribosylation Factor (ARF); ARF6; Dendritic Spine; Neuronal Activity; Phospholipase D; Rac1; Ras-related C3 Botulinum Toxin Substrate 1 (Rac1); Synaptic Plasticity