Disease relevance of NHA1

• Hypersensitivity to LiCl and improved growth in low K(+) are partly dependent on the Nha1p and Kha1p antiporters and on the Tok1p channel [1].
• Here, we show by co-precipitation of differently tagged Nha1p proteins expressed in the same cell that the yeast Nha1p l forms an oligomer [2].

High impact information on NHA1

• Hog1 phosphorylation stimulates Nha1 activity, and this is crucial for the rapid reassociation of proteins with their target sites in chromatin [3].
• Osmotic stress activates Hog1 MAP kinase, which phosphorylates at least two proteins located at the plasma membrane, the Nha1 Na+/H+ antiporter and the Tok1 potassium channel [3].
• Mutagenesis of the corresponding proline in the S. cerevisiae Nha1 antiporter (Pro146) confirmed that this proline of the fifth transmembrane domain is a critical residue for antiporter function [4].
• These observations suggest that Cos3p is a novel membrane protein that can enhance salinity-resistant cell growth by interacting with the C1+C2 domain of Nha1p and thereby possibly activating the antiporter activity of this protein [5].
• A novel membrane protein capable of binding the Na+/H+ antiporter (Nha1p) enhances the salinity-resistant cell growth of Saccharomyces cerevisiae [5].

Biological context of NHA1

• A search in its sequenced genome revealed two genes (designated as YlNHA1 and YlNHA2) with homology to the S. cerevisiae NHA1 gene, which encodes a plasma membrane alkali metal cation/H+ antiporter [6].
• A screening for loss-of-function mutations at the 775-980 carboxy-terminal tail of Nha1 has revealed a number of residues required for function in cell cycle, most of them clustering in two regions, from residues 869 to 876 (cluster A) and 918 to 927 (cluster B) [7].
• Mutagenesis analysis of the yeast Nha1 Na+/H+ antiporter carboxy-terminal tail reveals residues required for function in cell cycle [7].
• The DeltaC2-C6 form of C.t. Nha1p, containing only C1, restored the retarded cell growth at high salinity more than the control vector alone, but to a value lower than the wild type [8].
• Expression of various truncated forms of the C-terminal half of S.c. and C.t. Nha1p showed essentially the same phenotype for both species: deletion of the C4-C6 region caused cell growth to be more resistant to high salinity than the wild type, suggesting an inhibitory function of these domains on the antiporter activity [8].

Anatomical context of NHA1

• Cos3p-GFP mainly resides at the vacuole, but overexpression of Nha1p caused a portion of the Cos3p-GFP proteins to shift to the cytoplasmic membrane [5].
• We examined the molecular function of Nha1p by using secretory vesicles isolated from a temperature sensitive secretory mutant, sec4-2, in vitro [9].
• These results support the notion that Nha1p exists in membranes as a dimer and that the interaction of its monomers is important for its antiporter activity [2].

Associations of NHA1 with chemical compounds

• Overexpression of the NHA1 gene results in higher and partially pH-dependent tolerance to sodium and lithium; its disruption leads to an increased sensitivity towards these ions [10].
• Mutation of the conserved Asp residues Asp(266)-Asp(267) selectively abolished Na(+) efflux without modifying K(+) efflux and did not affect the capacity of Nha1 to relieve the G(1) blockage [11].
• These results suggest an essential role for C1 and an activating role of the C2-C3 region in the functional expression of Nha1 [8].
• The presence of the neighbouring part of the C-terminus (amino acids 883-928), rich in aspartate and glutamate residues, is necessary for the maintenance of maximum Nha1p activity towards sodium and lithium [12].
• We found that the entire Nha1p C-terminus domain is not necessary for either the proper localization of the antiporter in the plasma membrane or the transport of all four substrates (we identified rubidium as the fourth Nha1p substrate) [12].

Other interactions of NHA1

• Here we show that a hybrid protein composed of the Sod2 antiporter fused to the carboxy-terminal half of Nha1 strongly increased sodium tolerance, but did not allow growth at high potassium nor did rescue growth of the sit4 hal3 conditional mutant strain [7].
• Disruption of NHX1 or NHA1, encoding known Na(+)/H(+) antiporters, did not result in the loss of (22)Na(+) uptake or the alkaline cation-dependent DeltapH decrease [13].
• One of the transporters formerly believed to extrude K+ from the yeast cells (besides Ena1-4p and Nha1p) was named Kha1p and presumed as a putative plasma membrane K+/H+ antiporter [14].
• We propose that Nha1p regulates the potassium content of the cell and, as a consequence, can affect the activity of the main K(+) influx system (Trk1p) [15].

Analytical, diagnostic and therapeutic context of NHA1

• Co-immunoprecipitation assays then showed the inactive Nha1p-FLAG mutant interacted with the wild-type Nha1p-EGFP protein [2].

References