Disease relevance of Atp2b4

• Therefore, permanently transfected pheochromocytoma 12-derived cell lines were established that either over-expressed plasma membrane calcium ATPase isoform 4b, or suppressed the expression of the endogenous plasma membrane calcium ATPase isoform 4 [1].

High impact information on Atp2b4

• This acceleration of PMCA4 underlies the shortening of the action potential afterhyperpolarization produced by activation of bradykinin and purinergic receptors [2].
• Furthermore, the PMCA inhibitor 5-(and-6)-carboxyeosin diacetate succinimidyl ester reduced sperm motility in wild-type animals, thus mimicking the effects of PMCA4 deficiency on sperm motility and supporting the hypothesis of a pivotal role of the PMCA4 on the regulation of sperm function and intracellular Ca(2+) levels [3].
• The expression of the CII splice variant of the plasma membrane Ca(2+) ATPase 4 (PMCA4) was down-regulated in granule neurons when they were cultured under conditions of partial membrane depolarization (25 mM KCl), which are required for long term in vitro survival of the neurons [4].
• When granule cells were cultured in high concentrations of N-methyl-D-aspartic acid, a condition that increased cytosolic Ca2+ through the activation of glutamate-operated Ca2+ channels, up-regulation of PMCA1CII, 2, and 3 and down-regulation of PMCA4 was also observed [5].
• L-type Ca2+ channel blockers abolished both the up-regulation of the PMCA1CII, 2, and 3 isoforms and the down-regulation of PMCA4 isoform [5].

Biological context of Atp2b4

• Alternative splicing of both the 36 nt exon and a previously characterized 175 nt exon at splice site C, each of which can be either included or excluded in a highly tissue-specific manner, leads to the production of four different PMCA4 variants ranging in size from 1157 to 1203 amino acids [6].
• Furthermore, PMCA2 and PMCA4 underwent an evident time dependent up-regulation in astrocytes cultured in vitro [7].
• Pairwise comparisons reveal that the amino acid sequence of rPMCA4 has diverged substantially from those of rPMCA isoforms 1, 2 and 3 (73-76% identity) and from that of human PMCA4 (87%) [6].
• We have determined the primary structure of the rat plasma membrane Ca(2+)-ATPase isoform 4 (PMCA4), and have analysed its mRNA tissue distribution and alternative splicing patterns at splice site A [6].
• We now investigated the location of the mRNAs coding for isoforms PMCA3 and PMCA4 of Ca2+ pump in the nephron segments that are present in outer medullary parenchyma using the method of reverse transcription and polymerase chain reaction [8].

Anatomical context of Atp2b4

• Northern blot studies demonstrate that the PMCA4 mRNA is expressed in all rat tissues examined except liver, with the highest levels in uterus and stomach [6].
• A combination of PCR analysis of alternative splicing patterns and sequence analysis of the gene demonstrate that a 36 nt exon at site A is included in PMCA4 mRNAs of most tissues but is largely excluded in heart and testis [6].
• PMCA4 staining was restricted to a few cells showing intense labeling of the cell periphery and neurites [9].
• In most tissues the signal from the PMCA1 protein exceeded that of PMCA4, the exception being the erythrocyte [10].
• Two, PMCA1 and PMCA4, were expressed in all tissues tested (with the exception of the choroid plexus, where the former was not detected) [10].

Associations of Atp2b4 with chemical compounds

• Other genes including the PMCA2 and PMCA4 genes may code for PMCA proteins specific to Ca transporting tissues [11].

Other interactions of Atp2b4

• PMCA2 was also abundant in gray matter, except laminae I and II, while PMCA4 expression was restricted to the superficial layers of the dorsal horn [12].
• The relative quantities of PMCA1 and PMCA4 mRNA were not different in age-matched SHR vs. WKY rats, correlating with similar iCa2+ measurements [13].
• In mRNA extracted from whole dissected outer medulla we detected mRNA encoding three splice variants (a, b, and c) of isoform PMCA3; isoform PMCA4 was found in the outer medulla almost exclusively as variant b [8].
• RESULTS: We observed that in hypercalciuric LPD-fed rats, the mRNAs encoding isoforms PMCA2b and PMCA3(a + c) are significantly lower (Delta approximately-50%) than in HPD-fed hypocalciuric rats, whereas no changes in mRNAs encoding isoforms PMCA1b and PMCA4 were observed, and mRNA encoding calbindin 28 kDa was increased [14].

Analytical, diagnostic and therapeutic context of Atp2b4

• Isoform PMCA4 mRNA distribution in rat brain was studied by in situ hybridization using 33P-labeled antisense oligodeoxynucleotide probes [15].

References