Disease relevance of PMA1

• The yeast plasma membrane ATPase gene PMA1 was cloned into Escherichia coli using the high expression tac and T7 promoters [1].
• The Synechocystis ATPase (named PMA1) consists of 915 amino acids with a M(r) of 98,902; it has ten putative transmembrane domains and contains the conserved regions a to j common to all P-type ATPases [2].
• In addition ethanol (6-8%) causes the same two major changes to integral plasma-membrane protein composition that result from a sublethal heat stress, reduction in levels of the plasma membrane ATPase protein and acquisition of the plasma membrane heat-shock protein Hsp30 [3].
• BACKGROUND: Proton pump inhibitor-based therapy including two antibiotics is the treatment of choice for Helicobacter pylori infection [4].

High impact information on PMA1

• The strong homology between the amino-acid sequence encoded by PMA1 and those of (Na+ + K+), Na+-, K+- and Ca2+- ATPases is consistent with the notion that the family of cation pumps which form a phosphorylated intermediate evolved from a common ancestral ATPase [5].
• The function of the PMA1 gene is essential because a null mutation is lethal in haploid cells [5].
• We have cloned, mapped and sequenced the gene encoding the yeast plasma membrane ATPase (PMA1) and report here that it maps to chromosome VII adjacent to LEU1 [5].
• Bsd2 also controls the vacuolar targeting of a manganese transporter and a mutant plasma membrane ATPase, and together with the ER retrieval receptor Rer1, it protects cells from stress [6].
• Although Eps1 interaction with wild-type Pma1 was not detected, Eps1 co-immunoprecipitates with Pma1-D378N [7].

Biological context of PMA1

• PMA1 is an essential gene encoding the yeast plasma membrane [H(+)]ATPase [8].
• The previously unidentified MCM1 binding site in the essential PMA1 gene is required for expression of a PMA1:lacZ fusion gene, providing evidence that one site is functionally important [9].
• These studies further characterize the roles that URE2 and PMA1 play in regulating intracellular ion homeostasis [10].
• Physical, transcriptional and genetical mapping of a 24 kb DNA fragment located between the PMA1 and ATE1 loci on chromosome VII from Saccharomyces cerevisiae [11].
• A pma1-D378N mutant has a dominant-negative effect on cell growth because both newly synthesized mutant and wild-type Pma1 molecules are retained and degraded in the endoplasmic reticulum (ER) [8].

Anatomical context of PMA1

• Finally, we show that yeast expressing a constitutively active allele of calcineurin display pma1-like phenotypes, and that membranes from these yeast have decreased levels of Pma1p activity [10].
• We took advantage of a temperature-sensitive mutant in PMA1, encoding the plasma membrane ATPase, in which newly synthesized Pma1 is mislocalized to the vacuole via the endosome [12].
• We found that cytosol from an lst1-null strain supported the packaging of alpha-factor precursor into COPII vesicles but was deficient in the packaging of Pma1p, the essential plasma membrane ATPase [13].
• Interestingly, in an elo3delta mutant at 37 degrees C, newly synthesized Pma1p failed to enter raft domains early in the biosynthetic pathway, and upon arrival at the plasma membrane was rerouted to the vacuole for degradation [14].
• Although considerably more oxidation-resistant than other P-type ATPases, the yeast PMA1 H+-ATPase of Saccharomyces cerevisiae SY4 secretory vesicles was inactivated by H2O2, Fe2+, Fe- and Cu-Fenton reagents [15].

Associations of PMA1 with chemical compounds

• Deletion of APA1 causes a defective regulation of the PMA1 expression by glucose but has not noticeable effect on the expression of other TUF-regulated genes [16].
• PDR5 was solubilized with n-dodecyl-beta-D-malto-side and separated from the PMA1 plasma membrane H(+)-ATPase by glycerol gradient centrifugation [17].
• By contrast with wild-type Pma1, mutant Pma1-10 is hypophosphorylated and fails to associate with a Triton-insoluble fraction at 37 degrees C, suggesting failure to enter lipid rafts [18].
• We also show that calcineurin mutants are sensitive to aminoglycoside antibiotics such as hygromycin B while pma1 mutants are more resistant than wild type [10].
• Sorbic acid appeared to stimulate plasma membrane H+-ATPase activity in both PMA1 and pma1-205 [19].

Physical interactions of PMA1

• Furthermore, Pma1p coimmunoprecipitated with Lst1p and Sec24p from vesicles [13].
• The RPG sequences from PMA1 interact with the promoter binding factor TUF [20].

Enzymatic interactions of PMA1

• We present evidences indicating that Snf3p would be the sensor for the internal signal (phosphorylated sugars) of this pathway that would connect calcium signaling and activation of the plasma membrane ATPase [21].
• In vitro phosphorylation assays using a recombinant GST-fusion protein comprising 30 C-terminal amino acids of Pma1 suggest that Ser899 is phosphorylated by Ptk2 [22].

Regulatory relationships of PMA1

• The screening is based on the ability to abrogate the growth defect of cells suffering from the galactose induced Pdr3p driven over-expression of a dominant-lethal allele of the PMA1 gene placed under the control of the PDR5 promoter [23].
• On the other hand, ethanol activated the plasma membrane H(+)-ATPase activity from a strain expressing only the PMA1 ATPase but did not activate that from a strain expressing only the PMA2 ATPase [24].
• Cells carrying the wild-type PMA1 gene on the chromosome and a dominant lethal mutation under the control of a GAL1 promoter on a centromere-containing plasmid exhibit a galactose-dependent lethality [25].
• (Capieaux, E., Vignais, M.-L., Sentenac, A. and Goffeau, A. (1989). J. Biol. Chem. 264, 7437-7446), who show that the transcriptional factor TUF/RAP1 binds to upstream activating sequences in the PMA1 gene [26].
• Surprisingly, monomeric Pma1p present in ceramide-deficient membranes can be exported from the ER in COPII vesicles in a reaction that is stimulated by Lst1p [27].
• ATG19 was also able to suppress other dominant lethal PMA1 mutations [28].

Other interactions of PMA1

• A novel gene, AST1, identified by this selection, suppresses several pma1 alleles defective for targeting [29].
• As this pump is electrogenic, the activity of the Trk1 and -2 K+ uptake system is crucial for sustained Pma1p operation [30].
• The gene called PMA2 encodes a polypeptide of Mr = 102,157, which, with the exception of the 144 amino-terminal residues, is highly homologous to the structural gene PMA1 for the H+-ATPase [31].
• Examination of STE6 localization by indirect immunofluorescence indicates that STE6 is found in a punctate, possibly vesicular, intracellular pattern, distinct from the rim-staining pattern characteristic of PMA1 [32].
• Within a 31 kb region from PMA1 towards TRP5, a total of 12 transcription products ranging from 0.6 to 3.6 kb were identified in cells grown exponentially on rich medium [11].

Analytical, diagnostic and therapeutic context of PMA1

• The analysis of the PMA1 and PMA2 sequence alignment, compared with reported PMA1 mutations, points to a few residue substitutions as putative contributors to the observed kinetic changes [33].
• The expression of the PMA1 and PMA2 genes during Saccharomyces cerevisiae growth in medium with glucose plus increasing concentrations of ethanol was monitored by using PMA1-lacZ and PMA2-lacZ fusions and Northern blot hybridizations of total RNA probed with PMA1 gene [24].
• Localization by both immunofluorescence microscopy and cell fractionation shows that the export of Pma1p from the ER is impaired in lst1Delta mutants [34].
• The restriction map of the 5 kb HindIII fragment and Southern blot analysis reveal that the cloned fragment contains the entire structural gene for the plasma membrane ATPase and the 5' end of the adjacent LEU1 gene [35].
• Site-directed mutagenesis of the yeast PMA1 H(+)-ATPase. Structural and functional role of cysteine residues [36].

References