Disease relevance of Atp2b2

• However, the balance and hearing disorders of the deafwaddler mice appear to be less severe than homozygotes for a functionally null frameshift mutant or homozygous PMCA2 knockout mice, suggesting that deafwaddler PMCA2 retains some biological activity [1].

High impact information on Atp2b2

• Taken together, our findings suggest that glutamate, which recently has been implicated in EAE pathogenesis, suppresses neuronal PMCA2 expression leading to Ca(2+) dyshomeostasis at initial clinical phases [2].
• Moreover, exposure of spinal cord slice cultures to kainic acid significantly reduced PMCA2 mRNA levels [2].
• These conditions, which cause a chronic increase of the resting free Ca(2+) concentration in the neurons, have recently been shown to promote up-regulation of the PMCA2, 3, and 1CII isoforms [3].
• PMCA2 mRNAs are generated either by the inclusion of a 172-nucleotide exon, by the inclusion of both the 172-nucleotide exon and a 55-nucleotide exon, or by the exclusion of both exons [4].
• PMCA2 mRNAs are expressed predominantly in brain and heart, whereas PMCA3 mRNAs are expressed predominantly in brain and skeletal muscle [5].

Biological context of Atp2b2

• Furthermore, PMCA2 and PMCA4 underwent an evident time dependent up-regulation in astrocytes cultured in vitro [6].

Anatomical context of Atp2b2

• In contrast, astrocytes contain smaller amounts of PMCA2 [6].
• After spinal cord injury, the expression of PMCA2 was decreased; however, the change in expression of other isoforms showed a tendency of decrease but did not reach a statistically significant level [7].
• PMCA2 mRNA was highest in Purkinje cells of cerebellum and low in caudate-putamen, hypothalamic nuclei, habenula and choroid plexus [8].
• It exhibits 81% and 85% amino acid identity, respectively, to isoforms 1 and 2 (PMCA1 and PMCA2) of the plasma membrane Ca-ATPase [5].
• Within the dentate gyrus, PMCA 2 mRNA hybridized below control levels 4 h post-injection, but recovered to control levels by 24 h post-injection [9].

Associations of Atp2b2 with chemical compounds

• Taken together, the kinetic data suggest that the deafwaddler mutation affects PMCA2 by slowing the E(1)P to E(2)P transition, resulting in approximately 70% reduction in the PMCA2-mediated Ca(2+) export [1].
• A nucleotide substitution in deafwaddler results in a Gly to Ser transition at amino acid 283 in the small cytoplasmic loop of PMCA isoform 2 (PMCA2) [1].
• PMCA 2 is the isoform with the highest affinity for calmodulin, and has also been associated with high levels of inositol triphosphate [10].

Other interactions of Atp2b2

• By P10 (by postnatal day 10), most inner retinal PMCA consisted of PMCA2 and PMCA3 [11].
• This provides the first evidence for the presence of PMCA2 and PMCA3 isoforms at the protein level in non-neuronal tissue [12].

Analytical, diagnostic and therapeutic context of Atp2b2

• Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses, we have demonstrated PMCA1, -3, and -4, but not PMCA2, to be present in MC from these rat strains [13].
• When PMCA2 isoforms were immunoprecipitated from purified hair bundles of rat utricle, 2w was the only site A variant detected; moreover, immunocytochemistry for 2w in rat vestibular and cochlear tissues indicated that this splice form was located solely in bundles [14].
• Using immunofluorescence, we determined that PMCA2 is enriched in the stereocilia and present at a relatively low concentration in the kinocilium and in the remaining apical membrane [15].

References