MONaKA, a novel modulator of the plasma membrane Na,K-ATPase.
We have cloned and characterized mouse and human variants of MONaKA, a novel protein that interacts with and modulates the plasma membrane Na,K-ATPase. MONaKA was cloned based on its sequence homology to the Drosophila Slowpoke channel-binding protein dSlob, but mouse and human MONaKA do not bind to mammalian Slowpoke channels. At least two splice variants of MONaKA exist; the splicing is conserved perfectly between mouse and human, suggesting that it serves some important function. Both splice variants of MONaKA are expressed widely throughout the CNS and peripheral nervous system, with different splice variant expression ratios in neurons and glia. A yeast two-hybrid screen with MONaKA as bait revealed that it binds tightly to the beta1 and beta3 subunits of the Na,K-ATPase. The association between MONaKA and Na,K-ATPase beta subunits was confirmed further by coimmunoprecipitation from transfected cells, mouse brain, and cultured mouse astrocytes. A glutathione S-transferase-MONaKA fusion protein inhibits Na,K-ATPase activity from whole brain or cultured astrocytes. Furthermore, transfection of MONaKA inhibits 86Rb+ uptake via the Na,K-ATPase in intact cells. These results are consistent with the hypothesis that MONaKA modulates brain Na,K-ATPase and may thereby participate in the regulation of electrical excitability and synaptic transmission.
Mao
Hua
H
Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Ferguson
Tanya S
TS
Cibulsky
Susan M
SM
Holmqvist
Mats
M
Ding
Chunming
C
Fei
Hong
H
Levitan
Irwin B
IB
D017398:Alternative Splicing; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology* / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009434:Neural Pathways / Q000201:enzymology / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; C508328:MONaKA protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508327:PXK protein, human; D017346:Protein Serine-Threonine Kinases; D000254:Sodium-Potassium-Exchanging ATPase