详情页 - 首都医科大学宣武医院知识库

当前位置：首页 > 详情页

Aberrant trafficking of a Leu89Pro connexin32 mutant associated with X-linked dominant Charcot-Marie-Tooth disease

文献详情

资源类型：

WOS体系：

收录情况： ◇ SCIE

作者：

机构： [1]Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China, [2]Cell Therapy Center, Xuan Wu Hospital, Capital Medical University, and Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, China, [3]Department of Neurological Surgery, Wayne State University School of Medicine, Taylor, MI, USA, [4]Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China

出处：

DOI：

ISSN：

关键词： Charcot-Marie-Tooth disease CMT1X Connexin32 Gap junctions Leu89Pro

摘要：

Objective: To determine the functional abnormalities of the Leu89Pro mutation in connexin32 (CX32), which we have previously reported is present within an X-linked dominant Charcot-Marie-Tooth disease family. In this family, male patients were moderately to severely affected. Methods: We performed immunofluorescence to investigate whether the Leu89Pro CX32 protein was transported to the cell membrane in HeLa and Schwann cells. First, we constructed the eukaryotic express plasmids expressing CX32 (wild-type or Leu89Pro) and enhanced green fluorescent protein by the gene recombination technology. Then the recombinant plasmids were transiently transfected into communication-incompetent HeLa cells and human Schwann cells by the lipofectamine method. Later, we double-labeled cells for both CX32 and markers of the ER (calnexin) or the Golgi (58-kDa protein) at 24 h or 48 h. The images were collected using a Leica TCS SP5 II confocal microscope. Results: The mutant CX32 protein was localized in the endoplasmic reticulum and failed to reach the cell membrane to form gap junctions. Conclusion: Our results indicated that the Leu89Pro substitution in the second transmembrane domain of CX32 disrupts the trafficking of the protein, inhibiting the assembly of CX32 gap junctions, which in turn may result in peripheral neuropathy. This functional abnormality may explain the moderate to severe phenotype seen in Leu89Pro patients, and as such represents a promising therapeutic target in the treatment of this subset of CMTX patients.

基金：

语种：

被引次数：

WOS：

PubmedID：

中科院(CAS)分区：

出版当年[2015]版：

大类 | 4 区医学

小类 | 4 区临床神经病学 4 区神经科学

最新[2025]版：

大类 | 4 区医学

小类 | 4 区临床神经病学 4 区神经科学

JCR分区：

出版当年[2014]版：

Q4 CLINICAL NEUROLOGY Q4 NEUROSCIENCES

最新[2023]版：

Q3 CLINICAL NEUROLOGY Q4 NEUROSCIENCES

影响因子： 1.7 最新[2023版] 2.2 最新五年平均 1.439 出版当年[2014版] 1.481 出版当年五年平均 1.449 出版前一年[2013版] 1.418 出版后一年[2015版]

第一作者：

第一作者机构： [1]Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China, [*1]Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China.

通讯作者：

通讯机构： [*1]Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China. [*2]Xuan Wu Hospital, Capital Medical University, Beijing, China

推荐引用方式(GB/T 7714)：

APA：

MLA：

相关文献

[1]腓骨肌萎缩症X型临床、电生理及Connexin 32新突变一例 [2]Three novel mutations in a group of Chinese patients with X-linked Charcot-Marie-Tooth disease [3]腓骨肌萎缩症CMTX1型的间隙连接蛋白32基因突变检测 [4]Small heat-shock protein 22 mutated in autosomal dominant Charcot-Marie-Tooth disease type 2L [5]腓骨肌萎缩症X1型1个家系的临床、电生理和Connexin32基因突变分析 [6]A novel homozygous NDRG1 mutation in a Chinese patient with Charcot-Marie-Tooth disease 4D [7]Mutation analysis of the small heat shock protein 27 gene in Chinese patients with Charcot-Marie-Tooth disease [8]腓骨肌萎缩症基因重复异常的检测 [9]GJB1基因突变致CMTX1型一家系临床和电生理特征分析 [10]Characterization of genotype-phenotype correlation with MORC2 mutated Axonal Charcot-Marie-Tooth disease in a cohort of Chinese patients