A Novel Cx50 Insert Mutation from a Chinese Congenital Cataract Family Impairs Its Cellular Membrane Localization and Function

Xiukun Cui, Zheng Zhou, Keke Zhu, Ruiping Feng, Jiuli Han, Mengyuan Li, Shuangfeng Wang, Jing Li, Jing Zhang, Qiying Jiang, Wanting Zhang, Hongmei Mu, Yutao Liu, Yanzhong Hu

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Mutations in GJA8 are associated with hereditary autosomal dominant and recessive cataract formation. In this study, a novel insert mutation in GJA8 was identified in a Chinese congenital cataract family and cosegregated with the disease in this pedigree. This insert mutation introduces five additional amino acid residues YAVHY after histidine at the 95 site (p.H95_A96insYAVHY) within the second transmembrane (TM2) domain of Cx50 protein (Cx50-insert). Ectopic expression of Cx50-insert protein impairs the hemichannel functions and gap junction activity compared to wild-type Cx50 protein in human lens epithelial cells. Cx50-insert proteins were mislocated from cytoplasmic membrane to endoplasmic reticulum and lysosome. In mouse lens tissue, our results showed that Cx50 predominant expresses in epithelial cells and fiber cells at the transition zone of lens hinting its roles in lens differentiation. Taken together, these data suggest that the novel insert mutation in the TM2 domain of Cx50 protein, which impairs its trafficking to the cell membrane and gap-junction function, is associated with the cataract formation in this Chinese pedigree.

Original languageEnglish (US)
Pages (from-to)449-456
Number of pages8
JournalDNA and cell biology
Volume37
Issue number5
DOIs
StatePublished - May 1 2018

Keywords

  • Cx50
  • cataract
  • hemichannel function
  • insert mutation
  • membrane localization

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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    Cui, X., Zhou, Z., Zhu, K., Feng, R., Han, J., Li, M., Wang, S., Li, J., Zhang, J., Jiang, Q., Zhang, W., Mu, H., Liu, Y., & Hu, Y. (2018). A Novel Cx50 Insert Mutation from a Chinese Congenital Cataract Family Impairs Its Cellular Membrane Localization and Function. DNA and cell biology, 37(5), 449-456. https://doi.org/10.1089/dna.2017.4051