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Int. J. Mol. Sci. 2018, 19(8), 2214;

Regulation of Neuronal Na,K-ATPase by Extracellular Scaffolding Proteins

Science for Life Laboratory, Department of Women’s and Children’s Health, Karolinska Institutet, 17121 Solna, Sweden
Science for Life Laboratory, Department of Applied Physics, Royal Institute of Technology, 17121 Solna, Sweden
Institute of Chemical Biology and Fundamental Medicine, 630090 Novosibirsk, Russia
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 2 July 2018 / Revised: 24 July 2018 / Accepted: 25 July 2018 / Published: 29 July 2018
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Neuronal activity leads to an influx of Na+ that needs to be rapidly cleared. The sodium-potassium ATPase (Na,K-ATPase) exports three Na+ ions and imports two K+ ions at the expense of one ATP molecule. Na,K-ATPase turnover accounts for the majority of energy used by the brain. To prevent an energy crisis, the energy expense for Na+ clearance must provide an optimal effect. Here we report that in rat primary hippocampal neurons, the clearance of Na+ ions is more efficient if Na,K-ATPase is laterally mobile in the membrane than if it is clustered. Using fluorescence recovery after photobleaching and single particle tracking analysis, we show that the ubiquitous α1 and the neuron-specific α3 catalytic subunits as well as the supportive β1 subunit of Na,K-ATPase are highly mobile in the plasma membrane. We show that cross-linking of the β1 subunit with polyclonal antibodies or exposure to Modulator of Na,K-ATPase (MONaKA), a secreted protein which binds to the extracellular domain of the β subunit, clusters the α3 subunit in the membrane and restricts its mobility. We demonstrate that clustering, caused by cross-linking or by exposure to MONaKA, reduces the efficiency in restoring intracellular Na+. These results demonstrate that extracellular interactions with Na,K-ATPase regulate the Na+ extrusion efficiency with consequences for neuronal energy balance. View Full-Text
Keywords: lateral mobility; clustering; cross linking lateral mobility; clustering; cross linking

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Liebmann, T.; Fritz, N.; Kruusmägi, M.; Westin, L.; Bernhem, K.; Bondar, A.; Aperia, A.; Brismar, H. Regulation of Neuronal Na,K-ATPase by Extracellular Scaffolding Proteins. Int. J. Mol. Sci. 2018, 19, 2214.

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