Disease relevance of Atp2b1

• METHODS: Polyalkylcyanoacrylate nanoparticles (PMCA, PECA, PBCA and PIBCA nanoparticles) were assayed for their toxicity on peritoneal resident and thioglycolate-elicited macrophages [1].

High impact information on Atp2b1

• Inhibition of plasma membrane calcium-ATPase (PMCA) attenuated these effects, as did disruption by homologous recombination of the gene encoding PMCA4a and PMCA4b [2].
• CD22 cytoplasmic tyrosine residues were required for association with PMCA and enhancement of calcium efflux [2].
• The relative importance of plasma membrane Ca2+-ATPase (PMCA) 1 and PMCA4 was assessed in mice carrying null mutations in their genes (Atp2b1 and Atp2b4) [3].
• Loss of both copies of the gene encoding PMCA1 caused embryolethality, whereas heterozygous mutants had no overt disease phenotype [3].
• Our evidence indicates distinct isoform functions with the PMCA1 isoform involved in overall Ca(2+) clearance, while PMCA4 is essential for the [Ca(2+)](i) increase and contractile response to the CCh receptor-mediated signal transduction pathway [4].

Biological context of Atp2b1

• Targeted ablation of plasma membrane Ca2+-ATPase (PMCA) 1 and 4 indicates a major housekeeping function for PMCA1 and a critical role in hyperactivated sperm motility and male fertility for PMCA4 [3].
• These results provide further proof indicating up-regulation of the PMCA1 gene by multiple second messenger pathways [5].
• In mammals, there are 4 Pmca genes, and information on the cellular and tissue distribution of their expression during development will provide insight into the regulation and possible function of each Pmca isoform [6].
• PMCA nanoparticles in association with LPS significantly increase the expression of the inducible isoform of nitric oxide synthase, leading to the release of large amount of NO, which may be highly cytotoxic to the cultured cells in the presence of peroxide generated from the oxidative burst [1].
• Plasma membrane Ca2+ pumps (PMCA pumps) are Ca2+-Mg2+ ATPases that expel Ca2+ from the cytosol to extracellular space and are pivotal to cell survival and function [7].

Anatomical context of Atp2b1

• These results are consistent with an essential housekeeping or developmental function for PMCA1, but not PMCA4, and show that PMCA4 expression in the principle piece of the sperm tail is essential for hyperactivated motility and male fertility [3].
• KCl (80 mM) elicited both larger forces (150-190%) and increases in [Ca(2+)](i) (130-180%) in smooth muscle from Pmca1(+/-) and Pmca1(+/-)Pmca4(-/-) bladders than those in WT or Pmca4(-/-) [4].
• Mouse photoreceptors, cone bipolar cells and horizontal cells, which respond to light with a graded polarization, express isoform 1 (PMCA1) of the PMCA family [8].
• Calcineurin mediates repression of plasma membrane Ca2+-ATPase-4 (PMCA4) expression in neurons, whereas c-Myb is known to repress PMCA1 expression in vascular smooth muscle cells (VSMC) [9].
• The effect of differentiation on the RNA processing of the PMCA1 gene encoding a plasma-membrane Ca2+ pump and of the SERCA2 gene encoding a sarco(endo)plasmic reticulum Ca2+ pump was studied in the myogenic BC3H1 cell line [10].

Associations of Atp2b1 with chemical compounds

• The rise in half-times of force and [Ca(2+)](i) increases in response to KCl and CCh, and the concomitant half-times of their decrease upon washout of agonist were prolonged in Pmca4(-/-) (130-190%) and Pmca1(+/-)Pmca4(-/-) (120-250%) bladders, but not in Pmca1(+/-) bladders with respect to WT [4].
• The responses to carbachol (CCh: 10 muM) were also greater in Pmca1(+/-) (120-150%) than in WT bladders [4].
• Our results furthermore indicated that the myogenic RNA processing could be reversed for both types of Ca2+ pumps since the expression of the PMCA1 and SERCA2 muscle-specific messengers was rapidly down-regulated by cycloheximide treatment [10].
• In contrast, the alpha1 isoform (low ouabain affinity in rodents; IC(50) >10,000 nM), like the PMCA, is more uniformly distributed in these cells [11].
• Thus, the PMCA, with high affinity for Ca(2+) (K(d) congruent with 100 nM), may keep active zone Ca(2+) very low and thereby "reprime" the vesicular release mechanism following activity [11].

Other interactions of Atp2b1

• Phenotypes of SERCA and PMCA knockout mice [12].
• Gene manipulation did not alter the amounts of PMCA1, SERCA2, and NCX [13].

Analytical, diagnostic and therapeutic context of Atp2b1

• PMCA isoform-specific PCR primers generated appropriately sized products only for PMCA1 and PMCA4 from DCT cells but PMCA1-4 from whole mouse kidney [14].
• Northern blot analysis of mDCT cell RNA revealed transcripts of 7.5 and 5.5 kb for PMCA1 and 8.5 and 7.5 kb for PMCA4 [14].
• Using specific probes and in situ hybridization, we found that the four Pmca genes are expressed in spatially overlapping but distinct patterns in the mouse embryo [6].
• Using RT-PCR, mRNAs for InsP3Rs type-1, -2, and -3, PMCA-1 and -4, NCX-1, -2, and -3 could be detected [15].
• Our findings indicate that PMCA may be useful for the development of an ultra-sensitive diagnostic test to minimize the risk of further propagation of TSEs [16].

References