MONaKA, a Novel Modulator of the Plasma Membrane Na,K-ATPase
| Autor: | Hua Mao, Susan M. Cibulsky, Chunming Ding, Holmqvist Mats Harald, Hong Fei, Irwin B. Levitan, Tanya S. Ferguson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Immunoprecipitation
Nerve Tissue Proteins Biology Protein Serine-Threonine Kinases Mice Neural Pathways Animals Humans splice Na+/K+-ATPase Cloning Molecular Ion transporter Cells Cultured General Neuroscience Alternative splicing Cell Membrane Intracellular Signaling Peptides and Proteins Membrane Proteins Transfection Fusion protein Molecular biology Rats Alternative Splicing RNA splicing Synapses Sodium-Potassium-Exchanging ATPase Cellular/Molecular |
| Popis: | 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 theDrosophilaSlowpoke 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 β1 and β3 subunits of the Na,K-ATPase. The association between MONaKA and Na,K-ATPase β subunits was confirmed further by coimmunoprecipitation from transfected cells, mouse brain, and cultured mouse astrocytes. A glutathioneS-transferase-MONaKA fusion protein inhibits Na,K-ATPase activity from whole brain or cultured astrocytes. Furthermore, transfection of MONaKA inhibits86Rb+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. |
| Databáze: | OpenAIRE |
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