SUMOylation Pathways in Synaptic Development and Neurodegeneration
− この都医学研セミナーは終了しました。 −
| 演者 | Professor Dr. Paul Fraser（Medical Biophysics University of Toronto, Canada） |
|---|---|
| 会場 | 東京都医学総合研究所 2階講堂 |
| 日時 | 平成27年6月10日（水） 17：45 ～ 18：45 |
| 世話人 | 内原 俊記 副参事研究員（脳病理形態研究室） |
| 参加自由 | 詳細は下記問合せ先まで |
| お問い合わせ |
研究推進課 普及広報係 電話（03）5316－3109 |
講演要旨
Paul Fraser教授は家族性アルツハイマー病に関連するpresenilin遺伝子を同定したトロント大学の研究チームを率いて、その生化学的側面を次々に明らかにされました。今回シナプスの機能と形態変化についての最近の成果をお話しいただきます。
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 neurological disorders. We have generated a SUMO1 transgenic mouse model with 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 a number of 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 and others will be discussed which point to a significant contribution of SUMO1 modification on neuronal function which has implications for mechanisms involved in mental retardation and neurodegeneration.
SUMO1 Overexpression Affects Synaptic Function, Spine Density and Memory. Sci. Reports (in press) SUMOylation is an Inhibitory Constraint that Regulates the Prion-like Aggregation and Activity of CPEB3. Cell Reports (in press)
