8.A.118 The Na⁺K⁺-ATPase Beta-Subunit-Interacting NKAIN (NKAIN) Family 

Gorokhova et al. 2007 characterized a family consisting of four mammalian proteins (NKAIN1, 2, 3 and 4) and a single Drosophila ortholog dNKAIN with two well conserved N-terminal TMSs. NKAIN family members are neuronally expressed in multiple regions of the mouse brain, although their expression is not ubiquitous. Mouse NKAIN1 interacts with the beta1 subunit of the Na,K-ATPase, whereas the Drosophila ortholog dNKAIN interacts with Nrv2.2, a Drosophila homolog of the Na,K-ATPase beta subunits. NKAIN1 can form a complex with another beta subunit-binding protein, MONaKA, when binding to the beta1 subunit of the Na,K-ATPase. A complex between mammalian NKAIN1 and MONaKA may be required for NKAIN function. This hypothesis is supported by the fact that dNKAIN, but not NKAIN1, induces voltage-independent amiloride-insensitive Na⁺-specific conductance that can be blocked by lanthanum. Drosophila mutants with decreased dNKAIN expression exhibit temperature-sensitive paralysis, a phenotype also caused by mutations in the Na,K-ATPase α-subunit and several ion channels. The neuronal expression of NKAIN proteins, their membrane localization and the temperature-sensitive paralysis of NKAIN Drosophila mutants strongly suggest that this protein family may be critical for neuronal function (Gorokhova et al. 2007).