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Na/K‐ATPase α1 Isoform as a Critical Signal Integrator in Embryonic Development
Author(s) -
Wang Xiaoliang,
Zhang Jue,
Cui Xiaoyu,
Wang Jiayan,
Cai Liquan,
Pierre Sandrine V,
Xie Zijian
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1007.52
Subject(s) - embryogenesis , biology , embryo , phenotype , microbiology and biotechnology , mutant , somite , embryonic stem cell , gene isoform , chimera (genetics) , neurogenesis , genetics , gene
We have shown that Na/K‐ATPase interacts with caveolin‐1 through a putative caveolin‐binding motif, and regulates its trafficking in cell culture. The aim of this study is to review the importance of this putative interaction in animal physiology. A mCBM (F97A and F100A) mutant mouse was generated using a knock‐in strategy. Homozygosity of the mCBM Na/K‐ATPase animal results in embryonic lethality around mid‐gestation. Heterozygous animals were born with the expected Mendelian frequency and survived to adulthood. Further analysis of the embryonic development reveals the following defects. The first phenotype of homozygous embryos with obviously defect was noted at E7.0 day. At E9.0 day, homozygous embryos exhibited severe growth retardation with defective brain and somite development. By E12.5 day, the homozygous embryos were no longer detectable. On the other hand, heterozygous embryos seems to be normal through the development. However, they are significantly smaller in size at E9.0 day. Mechanically, RNAseq shows normal expression of different isoforms of Na/K‐ATPase and caveolin‐1. However, it reveals defects in Wnting signaling pathway, which results in severe down‐regulation of genes important for neurogenesis and muscle genesis. Those defects were further confirmed by qPCR analysis of mRNA from wild type and homozygous embryos. Taken together, our new findings suggest that α1 Na/K‐ATPase functions as a critical signal integrator in animal embryonic development, and that the putative caveolin‐binding motif is required for this non‐pumping function of Na/K‐ATPase. Support or Funding Information Marshall Institute for Interdisciplinary Research and NIH Grant HL‐109015