Investigation of the synergistic role of PLK2 and alpha-synuclein in the regulation of neuronal homeostasis and functions

PLK2 和 α-突触核蛋白在神经元稳态和功能调节中的协同作用研究

• 批准号: RGPIN-2016-05860
• 负责人: Oueslati, Abid
• 金额: $ 1.82万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630433
• 关键词: Investigation; synergistic; role; PLK2; alpha

Recent Progress: Alpha-synuclein (α-syn) is a small soluble protein localized at presynaptic terminals in the central nervous system. Although this protein is abundantly expressed in the brain (1% of total cytosolic protein), its exact physiological functions remain unknown. In the past decade, there has been an increasing interest for the role of phosphorylation in the regulation of α-syn normal function in vivo. In this context, our recent work identified Polo-like kinases (Plks) as the main kinases responsible for α-syn phosphorylation in vitro and in vivo. Moreover, we reported that Plk2, a member of Plk family, regulates α-syn selective clearance via the autophagy degradation pathway. However, the molecular mechanisms underlying Plk2-mediated α-syn clearance and the exact synergistic physiological role of these two proteins remain unknown.

最新进展：α-突触核蛋白(α-SYN)是一种定位于中枢神经系统突触前终末的小分子可溶性蛋白。虽然这种蛋白在大脑中大量表达(占总胞浆蛋白的1%)，但其确切的生理功能仍不清楚。在过去的十年里，人们对磷酸化在体内调节α-SYN正常功能中的作用越来越感兴趣。在这种背景下，我们最近的工作确定Polo-like kinase(Plk)是在体外和体内导致α-SYN磷酸化的主要激酶。此外，我们还报道了plk家族成员plk2通过自噬降解途径调节α-syn的选择性清除。然而，PLK2介导的α-SYN清除的分子机制以及这两种蛋白确切的协同生理作用仍不清楚。