Abstract
This chapter reveals a new unique story of Ca-signaling in upholding cellular homeostasis. The cytosolic activator (regulatory) protein, NaAF (of 170 kDa mass), for the ubiquitous P2-ATPase (and 80 kDa HAF solely for the gastric H/K-ATPase) is essential for P2-ATPase function. The NaAF and HAF function as the allosteric operator-cum gate-keeper of the dual channel P2-ATPase system (where mirror-image orientation of the two α-subunits serves as the membrane-embedded in-and-out gates) for simultaneous transport of two ions. The entire cyclic operation is in turn fine-tuned by local Ca (μM) as top (allosteric) controller of the P2-ATPase to maintain homeostasis. Thus at lower range Ca (<2) stimulates, but at higher range (>2) Ca abruptly inhibits the HAF-stimulated H/K-ATPase abolishing it at 4 μM Ca. At this point the (K ± HAF)-independent basal (Mg-dependent) activity of the H/K-ATPase acts as a provisional Ca-ATPase pump in an altered state to remove excess Ca, thus resuming the initial Ca-activated HAF-regulated state of a new cycle. Identical Ca-signaling operations also control the universal NaAF-regulated Na/K-ATPase system.
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Acknowledgements
The work was supported in part by the USPHS grant, AM19531, and RCDA (Research Career Development Award), AM 00623, from the NIH and Surgical Research Fund of SUNY-Upstate Medical Center, NY 13210. The author is currently involved in mind-body Research with Vivekananda Mind-Body Research Institute (VMBRI) associated with the Ramakrishna-Sarada Vedanta Center of Phoenix, Tempe, AZ 85281
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Ray, T. (2016). Calcium Controls the P2-ATPase Mediated Homeostasis: Essential Role of NaAF. In: Chakraborti, S., Dhalla, N. (eds) Regulation of Membrane Na+-K+ ATPase. Advances in Biochemistry in Health and Disease, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-319-24750-2_4
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