The Role of P-type ATPases in Health and Diseases

Dear Colleagues,

P-type ATPases are a large group of related pumps that hydrolyze ATP to perform the active transport of ions or phospholipids across cellular membranes. All P-type ATPases form a transient phosphorylated intermediate at the key conserved aspartate residue within the pump during a catalytic cycle. The ion pumps create electrochemical gradients that are essential for transepithelial transport, nutrient uptake and the regulation of the membrane potential and cell volume. In addition, they mediate intracellular signaling and intercellular adhesion. Phospholipid flippases regulate the asymmetric lipid distribution across the lipid bilayer and are critical for the biogenesis of cell membranes and for important processes such as apoptosis and thrombus formation.

Dysfunctions of P-type ATPases are known to contribute to various diseases. Mutations in the alpha2 and alpha3 subunits of Na,K-ATPase are associated with neurological diseases, including rapid-onset dystonia–parkinsonism, and mutations in the alpha1 subunit of the Na,K-ATPase have been found to cause Charcot–Marie–Tooth type 2 disease. The malfunctioning of the Ca-ATPases contributes to hypertension and neurodegenerative diseases, and mutations in this pump can cause cardiac dysfunction, deafness, hypertension, cerebellar ataxia, heart failure, Brody myopathy and Darier disease. Mutations in the Cu-ATPases cause Menkes and Wilson diseases. Deficiencies in phospholipid flippases have been linked to progressive familial intrahepatic cholestasis, obesity, diabetes, hearing loss and neurological diseases. Recent studies have shown that the severity of disease symptoms does not always correlate with the degree of the loss of transport activity due to mutations, suggesting that misfolding during biosynthesis and following unfolded protein response significantly contribute to pathogenicity separately from the functional impairment of the pump.

For this research topic, we aim to present an update on the structure and function of P-type ATPases, with an emphasis on newly identified functions of well-characterized pumps, the emerging functions of less known P-type ATPases, novel experimental approaches to study these enzymes and the mechanisms of disease-causing genetic mutations. We encourage the submission of expert opinions, commentaries, reviews and manuscripts describing original data.

Dr. Olga Vagin
Dr. Sigrid A. Langhans
Dr. Laura Dada
Guest Editors

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• P-type ATPases
• Na,K-ATPase
• H-ATPase
• H,K-ATPase
• Ca-ATPase
• Cu-ATPase
• phospholipid flippases
• genetic disease