title: SUMO1 Affects Synaptic Function, Spine Density and Memory.
abstract: Small ubiquitin-like modifier-1 (SUMO1) plays a number of roles in cellular events and recent evidence has given momentum for its contributions to neuronal development and function. Here, we have generated a SUMO1 transgenic mouse model with exclusive overexpression in neurons in an effort to identify in vivo conjugation targets and the functional consequences of their SUMOylation. A high-expressing line was examined which displayed elevated levels of mono-SUMO1 and increased high molecular weight conjugates in all brain regions. Immunoprecipitation of SUMOylated proteins from total brain extract and proteomic analysis revealed ~95 candidate proteins from a variety of functional classes, including a number of synaptic and cytoskeletal proteins. SUMO1 modification of synaptotagmin-1 was found to be elevated as compared to non-transgenic mice. This observation was associated with an age-dependent reduction in basal synaptic transmission and impaired presynaptic function as shown by altered paired pulse facilitation, as well as a decrease in spine density. The changes in neuronal function and morphology were also associated with a specific impairment in learning and memory while other behavioral features remained unchanged. These findings point to a significant contribution of SUMO1 modification on neuronal function which may have implications for mechanisms involved in mental retardation and neurodegeneration.
authors.affiliation: 1] Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard Avenue, Toronto, M5T 2S8, Ontario [2] Molecular Brain Science, United Graduate School of Child Development, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan [3] Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan [4] Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Matsuzaki
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St.New York, 10032, NY.
authors.forename: Linda
authors.initials: L
authors.lastname: Lee
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard Avenue, Toronto, M5T 2S8, Ontario.
authors.forename: Erin
authors.initials: E
authors.lastname: Knock
authors.affiliation: 1] Ontario Cancer Institute, University Health Network [2] Departments of Medical Biophysics, Laboratory Medicine and Pathobiology University of Toronto.
authors.forename: Tharan
authors.initials: T
authors.lastname: Srikumar
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St.New York, 10032, NY.
authors.forename: Mikako
authors.initials: M
authors.lastname: Sakurai
authors.affiliation: 1] Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard Avenue, Toronto, M5T 2S8, Ontario [2] Departments of Medical Biophysics, Laboratory Medicine and Pathobiology University of Toronto.
authors.forename: Lili-Naz
authors.initials: LN
authors.lastname: Hazrati
authors.affiliation: Molecular Brain Science, United Graduate School of Child Development, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St.New York, 10032, NY.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Staniszewski
authors.affiliation: 1] Ontario Cancer Institute, University Health Network [2] Departments of Medical Biophysics, Laboratory Medicine and Pathobiology University of Toronto.
authors.forename: Brian
authors.initials: B
authors.lastname: Raught
authors.affiliation: Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St.New York, 10032, NY.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio
authors.affiliation: 1] Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard Avenue, Toronto, M5T 2S8, Ontario [2] Departments of Medical Biophysics, Laboratory Medicine and Pathobiology University of Toronto.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Fraser
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D002478:Cells, Cultured; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D040901:Proteomics; D025842:SUMO-1 Protein / Q000235:genetics* / Q000378:metabolism; D058207:Sumoylation / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics; D050863:Synaptotagmin I / Q000378:metabolism
chemical_list: D025842:SUMO-1 Protein; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse