期刊论文

Calcium Homeostasis Modulator 2 Q87A Mutation Promotes Depression Susceptibility

中文

生物化学与生物物理进展

1000-3282

2021

48

12

1439-1447

10.16476/j.pibb.2021.0048

81930029:国家自然科学基金 81630026:国家自然科学基金 81501200:国家自然科学基金 7161009:北京市自然科学基金资助项目

本校为第一机构

钙稳态调节蛋白2(calcium homeostasis modulator 2,Calhm2)参与钙离子活动和ATP释放的调控.本实验室的前期工作已经证实,Calhm2可以介导星形胶质细胞ATP的释放,在抑郁症的发生发展中起到重要作用.为了进一步探究Calhm2在抑郁症发生发展中的分子机制,本文首先预测了Calhm2的ATP结合位点,即位于第87位点的谷氨酰胺(Q87),并将其突变为丙氨酸(A),建立了一个携带calhm2突变(Q87A)的小鼠品系.随后,通过对原代星形胶质细胞的胞内和胞外ATP检测,发现Calhm2 Q87A突变导致星形胶质细胞ATP的释放下降;此外,通过对小鼠大脑海马切片的ATP检测,发现Calhm2 Q87A突变小鼠海马组织的ATP释放较正常小鼠下降;最后,...

Calcium homeostasis modulator 2(Calhm2)is involved in the modulation of Ca~(2+) activity and ATP release.Our previous work has demonstrated that Calhm2 plays a crucial role in the progression of depression by regulating the astrocytic ATP release.In order to further explore the role and mechanism of Calhm2 in the development of depression, we firstly predicted the ATP binding site(glutamine, amino acid 87)of Calhm2, and established a mouse line that carried calhm2 mutation by mutating the glutamine to alanine(Q87A).Secondly, by using the primary culture of astrocyte and ATP detection analysis,...