Cell biology and dynamics of Neuronal Na+/K+-ATPase in health and diseases

Abstract

Neuronal Na⁺/K⁺-ATPase is responsible for the maintenance of ionic gradient across plasma membrane. In doing so, in a healthy brain, Na⁺/K⁺-ATPase activity accounts for nearly half of total brain energy consumption. The α3-subunit containing Na⁺/K⁺-ATPase expression is restricted to neurons. Heterozygous mutations within α3-subunit leads to Rapid-onset Dystonia Parkinsonism, Alternating Hemiplegia of Childhood and other neurological and neuropsychiatric disorders. Additionally, proteins such as α-synuclein, amyloid-β, tau and SOD1 whose aggregation is associated to neurodegenerative diseases directly bind and impair α3-Na⁺/K⁺-ATPase activity. The review will provide a summary of neuronal α3-Na⁺/K⁺-ATPase functional properties, expression pattern, protein-protein interactions at the plasma membrane, biophysical properties (distribution and lateral diffusion). Lastly, the role of α3-Na⁺/K⁺-ATPase in neurological and neurodegenerative disorders will be discussed. This article is part of the special issue entitled 'Mobility and trafficking of neuronal membrane proteins'.

Keywords: ATP1A3 disorders; Alzheimer's disease; Na(+)/K(+)-ATPase; Parkinson's disease; neurodegeneration.