March 2010

Jerry Lingrel: Pumping Out Great Science

Then, in 1976, the University of Cincinnati’s microbiology department hired a new faculty member, Dennis Lang, who ended up becoming one of Lingrel’s neighbors. Given their similar destination, the two ended up carpooling on numerous occasions. And through this ridesharing, Lingrel was introduced to another molecular black box: the Na,K-ATPase, which pumps potassium into and sodium out of a cell.

“Lang had done his graduate studies under Efraim Racker at Cornell, who was a leading expert on the Na,K-ATPase,” Lingrel says, “and, during our rides, he kept telling me how important this enzyme was in biology. So, one day I asked him what they knew about the ATPase structure, and he responded that they didn’t even know the amino acid sequence yet.”

That sparked an idea: Lingrel admittedly knew very little about transport proteins, but what he did know was molecular cloning.


One of Jerry Lingrel’s many discoveries regarding Na,K-ATPase was uncovering the sperm-specific α4 isoform, revealed in A as being localized to the mid-piece region of the flagellum. B shows a control sperm with only secondary antibody staining. Woo, A. L., et al. J. Biol. Chem. (2000) 275, 20693–20699.

“I thought to myself: Oh, our lab could handle that; and if this ATPase is as important as Lang believes, then sequencing and characterizing it would be a tremendous advance to science.”

Working with membrane proteins would be tricky, but Lingrel always has operated with a simple belief: If you take the time to think about a problem and pick the right system to work on it, there’s no reason a project should not work. So, he picked sheep kidney cells, an abundant source of Na,K-ATPase, and, together with a very talented postdoc, Gary Shull, he managed to isolate ATPase mRNA, make cDNA clones, decipher the amino acid sequence for the α and β subunits and identify important residues for pump activity. 

“It ended up that we published our ATPase sequence in the exact same issue of Nature that David MacLennan reported his sequence for the calcium ATPase,” Lingrel says. “So, in one day, we managed to open up a whole new era in the study of ion transport proteins.”

Lingrel would go on to make countless more discoveries regarding Na,K-ATPase, including showing that the catalytic α subunit had four separate isoforms which contributed to the numerous functions the pump had throughout the body. For example, the α4 isoform is found exclusively in sperm and helps sperm cells move, whereas the α2 and α3 isoforms are highly expressed in brain cells and produce learning deficiencies when knocked out in mice. 

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