Landmark study reveals first genetic evidence of sodium pump’s essential function

HUNTINGTON, W.Va. – New findings offer the first genetic evidence that the sodium pump is essential for animal organ development, according to a study led by Marshall University scientists that involves the scaffolding, or signaling, function of the sodium pump. 

The research, published May 27 in Science Advances, indicates that a gene sequence in the sodium pump, also known as Na/K-ATPase, is critical to embryonic development in animals. The short sequence of DNA identified in the study is nearly identical in worms, fish, chickens, birds or mammals, including humans. The sequence, called the caveolin binding motif, is required for the sodium pump to be a receptor. 

“The sodium pump cannot signal without the sequence, meaning the brain cannot fully develop,” said first and corresponding author, Xiaoliang Wang, M.D., Ph.D., a postdoctoral research fellow at the Marshall University Joan C. Edwards School of Medicine. “Without this function, a human stem cell can’t become a stem cell.” 

The sodium pump, also known as Na/K-ATPase, is expressed in nearly every cell in the body and maintains the sodium-potassium gradient across the cell membrane. This study builds upon the seminal work of the late Zijian Xie, Ph.D., who, along with collaborators, discovered the signaling & scaffolding function of the Na/K-ATPase in the late 1990s. Xie’s discovery has had tremendous applications in both cell biology and medicine and opened the door to this new area of research. 

Wang along with co-first author, Liquan Cai, Ph.D., and researchers at the Marshall Institute for Interdisciplinary Research and Joan C. Edwards School of Medicine, used basic biochemistry and gene modification technology to generate three models that allowed the team to explore the essential role of the protein in various animal species.

“By understanding these basic pathways, we can develop genetic or pharmacological approaches to try to address untreatable symptom complexes,” said Joseph I. Shapiro, M.D., dean of the Marshall University Joan C. Edwards School of Medicine, who has been Xie’s primary research partner for the past two decades. “The gap between understanding these basic pathways and applying them to health and disease is getting shorter. If we can better understand how the scaffolding function of the sodium pump is related to the development of diseases like pulmonary hypertension, obesity and diabetic retinopathy, we are better suited to treat them.” 


This research was supported by funds provided by (1) the BrickStreet Foundation, (2) the Huntington Foundation and (3) the National Institutes of Health (NIH) (R15 HL 145666). The work was reviewed and approved by the Marshall University Institutional Animal Care and Use Committee.

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Date Posted: Friday, June 26, 2020