假定蛋白质激酶Stk36通过与Ulk4结合,对纤维生成和脑脊液流动至关重要
Hongye Zhang1, Meimei Yang2, Jianhua Zhang1
1Ministry of Education Key Laboratory of Molecular and Cellular Biology, Hebei Research Center of the Basic Discipline of Cell Biology, Hebei Key Laboratory of Molecular and Cellular Biology, Hebei Collaboration Innovation Center for Cell Signaling and Environmental Adaptation, College of Life Sciences, Hebei Normal University, Shijiazhuang, China.
概括
血清/氨酸激酶36 (STK36) 和Unc51-like-kinase 4 (ULK4) 对脑脊液 (CSF) 流动至关重要. 这些蛋白质相互作用,调节运动的功能,并预防水头,一种与毛缺陷相关的疾病.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
背景情况:
- 脑脊液 (CSF) 流动过程中,表皮细胞上的移动性纤毛是必不可少的,它们的功能障碍与水脑有关.
- 以前,Unc51-like-kinase 4 (ULK4) 与CSF流动和运动性纤维生成有关,但潜在的机制尚不清楚.
- ULK4 低形变异基因突变体表现出水头,这是由于毛生殖缺陷和毛动力的受损.
研究的目的:
- 调查ULK4对象的氨酸/氨酸激酶36 (STK36) 在运动毛功能和CSF流动中的作用.
- 阐明ULK4和STK36调节纤毛发育和纤毛功能的分子机制.
主要方法:
- 酵母二杂交 (Y2H) 试验表明STK36和ULK4.4之间的直接相互作用.
- 在HEK293T细胞中进行共免疫沉降 (co-IP) 试验,以确认STK36-ULK4相互作用.
- 对STK36低形态突变小鼠 (Stk36tmE4-/-) 的分析,用于脑水,脑脊液流动,状结构和基因表达.
主要成果:
- STK36通过它们的N端激酶域直接与ULK4相互作用.
- Stk36tmE4-/-小鼠表现出渐进的水头发症,功能障碍的脑脊液流动,以及多个移动毛缺陷,反映了Ulk4tm1a/tm1a表型.
- STK36的缺陷会破坏Foxj1转录因子表达和其他与纤毛发育相关的基因.
结论:
- 像ULK4一样,STK36对于维持CSF流动和适当的肌功能至关重要.
- STK36和ULK4通过直接结合合作,调节Foxj1介导的途径,这对于纤毛发育和纤毛功能至关重要.
- 这些发现表明,涉及STK36和ULK4的纤毛发育和纤毛功能存在保存的分子机制,可能适用于其他甲基动物.
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