Human alpha3 beta1 isoform of Na+/K+‐ATPase: expression in yeast, mutations and their relation to neurological disorders

Abstract

The Na+/K+‐ATPase (NKA) is a crucial membrane protein responsible for maintaining the membrane potential by actively transporting sodium and potassium ions. The proper function of this pump is essential for all cells (e. g. in homeostasis, membrane potential). The human body contains four isoforms of this enzyme, which are spread over whole organism. One of the most important localizations of NKA is the brain. Medical research of Heinzen et al. (2014) suggests that there is a possible connection between NKA alpha3 isoform mutations (mainly D801N, E815K, D923N, D923Y and G947R) and neurological disorders. Detailed studies of patient's genome revealed that all these mutations are closely linked to Rapid‐Onset Dystonia Parkinsonism and Alternating Hemiplegia of Childhood.Modern biotechnological methods, especially the production of a heterologous protein in expression systems, enable deeper study of a wide range of non‐abundant proteins. The preparation of alpha3 NKA proteins (wild type and mutants) was performed according to Pedersen et al. (2006) with some modifications. In general, changes in the level of protein expression and determination of the relative enzyme activity could be the first step towards better understanding of the relation between NKA function and neurological disorders.Support or Funding InformationThis project was supported by grant No. L01204 (Sustainable development of research in the Centre of the Region Haná) from the National Program of Sustainability I, MEYS and by “Palacky University Foundation 2015”. The project was awarded by EMBO Short‐Term fellowship ASTF 243‐2015.