title: Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization.
abstract: Neuroligin (NLG) 1 is important for synapse development and function, but the underlying mechanisms remain unclear. It is known that at least some aspects of NLG1 function are independent of the presynaptic neurexin, suggesting that the C-terminal domain (CTD) of NLG1 may be sufficient for synaptic regulation. In addition, NLG1 is subjected to activity-dependent proteolytic cleavage, generating a cytosolic CTD fragment, but the significance of this process remains unknown. In this study, we show that the CTD of NLG1 is sufficient to (a) enhance spine and synapse number, (b) modulate synaptic plasticity, and (c) exert these effects via its interaction with spine-associated Rap guanosine triphosphatase-activating protein and subsequent activation of LIM-domain protein kinase 1/cofilin-mediated actin reorganization. Our results provide a novel postsynaptic mechanism by which NLG1 regulates synapse development and function.
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China.
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China Institute of Life Sciences, The Collaborative Innovation Center for Brain Science, Southeast University, Nanjing 210096, China.
authors.forename: Zikai
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Dang
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Qi
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China.
authors.forename: Guiqin
authors.initials: G
authors.lastname: He
authors.affiliation: Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Celeste
authors.initials: C
authors.lastname: Leung
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington, DC 20007.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pak
authors.affiliation: Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada zhengping.jia@sickkids.ca wei.xie@seu.edu.cn.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China Institute of Life Sciences, The Collaborative Innovation Center for Brain Science, Southeast University, Nanjing 210096, China zhengping.jia@sickkids.ca wei.xie@seu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
mesh_terms: D008841:Actin Cytoskeleton / Q000201:enzymology*; D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology*; D049229:Dendritic Spines / Q000201:enzymology*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005838:Genotype; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D054461:Lim Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D010641:Phenotype; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D015398:Signal Transduction; D013569:Synapses / Q000201:enzymology*; D013997:Time Factors; D014162:Transfection; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D015816:Cell Adhesion Molecules, Neuronal; D020690:GTPase-Activating Proteins; C543508:Sipa1l1 protein, mouse; C093438:neuroligin 1; D054461:Lim Kinases; C515893:Limk1 protein, mouse; C095325:Limk2 protein, mouse; D020827:rap1 GTP-Binding Proteins