Nucleoporin 35 regulates cardiomyocyte pH homeostasis by controlling Na^(+)-H^(+)exchanger-1 expression

作     者：Liang Xu Lei Pan Jun Li Bijun Huang Jing Feng Changming Li ShiyiWang Erlinda The Yuan Liu Tianyou Yuan Lixiao Zhen Dandan Liang Yi Liu Li Li Yingyu Cui Xiaoyan Jiang Luying Peng Yi-Han Chen 

作者机构：Key Laboratory of Arrhythmias of the Ministry of Education of ChinaShanghai East HospitalTongji University School of MedicineShanghai 200120China Research Center for Translational MedicineShanghai East HospitalTongji University School of MedicineShanghai 200120China Institute of Medical GeneticsTongji UniversityShanghai 200092China Department of CardiologyShanghai East HospitalTongji University School of MedicineShanghai 200120China Department of Pathology and PathophysiologyTongji University School of MedicineShanghai 200092China 

出 版 物：《分子细胞生物学报:英文版》 (Journal of Molecular Cell Biology)

年 卷 期：2015年第7卷第5期

页      面：476-485页

核心收录：

学科分类：02[经济学] 0202[经济学-应用经济学] 020206[经济学-国际贸易学] 

基　　金：This work was supported by grants from the National Key Basic Research Program of China(2013CB531100 to Y.-H.C.) the National Natural Science Foundation of China for National Innovative Research Groups(81221001 to Y.-H.C.) the Major International Joint Research Program of China(81120108004 to Y.-H.C.) the Youth Program(81100124 to L.X.) the General Program(81170224 and 81270313 to J.L.and 31271214 to Y.-H.C.)of the National Natural Science Foundation of China 

主　　题：cardiomyocyte intracellular pH Na^(+)-H^(+)exchanger nuclear pore complex nucleo-cytoplasmic transport 

摘      要：The mammalian nuclear pore complex is comprised of∼30 different nucleoporins(Nups).It governs the nuclear import of gene expression modulators and the export of *** cardiomyocytes,Na1-H1 exchanger-1(NHE1)is an integral membrane protein that exclusively regulates intracellular pH(pHi)by exchanging one intracellular H1 for one extracellular ***,the role of Nups in cardiac NHE1 expression remains *** herein report that Nup35 regulates cardiomyocyte NHE1 expression by controlling the nucleo-cytoplasmic trafficking of nhe1 *** N-terminal domain of Nup35 determines nhe1 mRNA nuclear export by targeting the 5′-UTR(2412 to2213 nt)of ***35 ablationweakensthe resistance of cardiomyocytes to an acid challenge by depressingNHE1 ***,we identify thatNup35 andNHE1 are simultaneously downregulated in ischemic cardiomyocytes both in vivo and in *** expression of Nup35 effectively counteracts the anoxia-induced intracellular *** conclude that Nup35 selectively regulates cardiomyocyte pHi homeostasis by posttranscriptionally controlling NHE1 *** finding reveals a novel regulatory mechanism of cardiomyocyte pHi,and may provide insight into the therapeutic strategy for ischemic cardiac diseases.