Analysis of the tissue-specific distribution of mRNAs encoding the plasma membrane calcium-pumping ATPases and characterization of an alternately spliced form of PMCA4 at the cDNA and genomic levels (original) (raw)
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Molecular Brain Research, 1997
Calcium in its ionized form (Cii' ' 1 is the nlw4 L'orliillon and arguably the most important signal transducer in cukaryotic cells. Unlike most cellular messengers, calcium cannot be broken down. it must eventually hc rcmovt~l from thlr cell. Unchecked accumulation 01' cal~;ium within ;I cell is 'toxic and will WWitlUllly lead to the dealh of the cell. In the brain, there are numerous examples in which chronically elevated calcium levels are believed to he causally linked to eventual cell death in certain populations of neurons which display differential Ca' + susceptibility for poorly understood reasons [8,13. I S]. One of the critical components of the machinery responsible for maintaining homeostatic levels of intracellular Ca'+ is the Ca' +-ATPase of the plasma membrane (PMCA). In humans and other mammals, multiple PMCA isoforms are encoded by four separate genes loc..lized on different chromosomes 1271. Alternative RNA splicing adds further diversity to the PMCA protein family. The PMCAs belong to the superfarniiy of P-type transport ATPases [22]
Primary structure of human plasma membrane Ca2+-ATPase isoform 3
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1996
The complete coding sequence of the human plasma membrane calcium ATPase (PMCA) isoform 3 was determined from overlapping genomic and cDNA clones. The cDNAs for the two major alternative splice variants 3a (3CII) and 3b (3CI) code for proteins of 1173 and 1220 amino-acid residues, respectively, which show 98% identity with the corresponding rat isoforms. On a multiple human tissue Northern blot, a major PMCA3 transcript of about 7 kb was detected exclusively in the brain, demonstrating the highly restricted pattern of expression of this isoform to human neuronal tissues. With the elucidation of the human PMCA3 primary structure, complete sequence information is now available for the entire family of human PMCA isoforms.
The plasma membrane Ca 2+ ATPase of animal cells: Structure, function and regulation
Archives of Biochemistry and Biophysics, 2008
Most important processes in cell life are regulated by calcium (Ca 2+ ). A number of mechanisms have thus been developed to maintain the concentration of free Ca 2+ inside cells at the level (100-200 nM) necessary for the optimal operation of the targets of its regulatory function. The systems that move Ca 2+ back and forth across membranes are important actors in its control. The plasma membrane calcium ATPase (PMCA pump) which ejects Ca 2+ from all eukaryotic cell types will be the topic of this contribution.
Plasma Membrane Ca2+ Pump PMCA4z Is More Active Than Splicing Variant PMCA4x
Frontiers in Cellular Neuroscience, 2021
The plasma membrane Ca2+ pumps (PMCA) are P-ATPases that control Ca2+ signaling and homeostasis by transporting Ca2+ out of the eukaryotic cell. Humans have four genes that code for PMCA isoforms (PMCA1-4). A large diversity of PMCA isoforms is generated by alternative mRNA splicing at sites A and C. The different PMCA isoforms are expressed in a cell-type and developmental-specific manner and exhibit differential sensitivity to a great number of regulatory mechanisms. PMCA4 has two A splice variants, the forms “x” and “z”. While PMCA4x is ubiquitously expressed and relatively well-studied, PMCA4z is less characterized and its expression is restricted to some tissues such as the brain and heart muscle. PMCA4z lacks a stretch of 12 amino acids in the so-called A-M3 linker, a conformation-sensitive region of the molecule connecting the actuator domain (A) with the third transmembrane segment (M3). We expressed in yeast PMCA4 variants “x” and “z”, maintaining constant the most frequent...
Hearing Research, 2007
Ca 2+ ions play a pivotal role in inner ear hair cells as they are involved from the mechano-electrical transduction to the transmitter release. Most of the Ca 2+ that enters into hair cells via mechano-transduction and voltage-gated channels is extruded by the plasma membrane Ca 2+ -ATPases (PMCAs) that operate in both apical and basal cellular compartments. Here, we determined the identity and distribution of PMCA isoforms in frog crista ampullaris: we showed that PMCA1, PMCA2 and PMCA3 are expressed, while PMCA4 appears to be negligible. We also identify PMCA1bx, PMCA2av and PMCA2bv as the major splice variants produced from PMCA1 and PMCA2 genes. PMCA2av appears to be the major Ca 2+ -pump operating at the apical pole of the cell, even if PMCA1b is also expressed in the stereocilia. PMCA1bx is, instead, the principal PMCA of hair cell basolateral compartment, where it is expressed together with PMCA2 (probably PMCA2bv) and PMCA3.
European Journal of Biochemistry, 1992
cDNA species covering the entire coding sequence of the human homologue of the rat plasma membrane Ca2 +-ATPase (PMCA) isoform 2 have been isolated and characterized. The deduced amino acid sequence shows 99% identity with that of the rat protein and can be aligned with the latter without gaps except for one 14-amino-acid-residue insert in the region immediately preceding the putative phospholipid-sensitive domain in the human pump. cDNA clones isolated by anchored polymerase-chain reaction revealed additional microheterogeneity in the same N-terminal PMCA2coding region. Alternative RNA splicing involving a region of 135 nucleotides generates three types of cDNA. One does not contain any of the 135 bp, and the other two contain 42 bp or the entire 135 bp of the optional sequence. Analysis of genomic DNA indicates that this sequence is encoded by three separate exons of 33, 60 and 42 bp. Although each of these exons could be inserted into the mRNA without changing the reading frame, polymerase-chain amplifications using cDNA libraries from several human tissues show that the 33-bp and the 60-bp exons are never independently used during splicing. The unequal distribution of the splice variants suggests tissue-specific regulation of the alternative-splicing pathways and indicates a functional specialization of the encoded isoform subtypes.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2004
The distribution of the secretory pathway Ca 2 +-ATPase (SPCA1) was investigated at both the mRNA and protein level in a variety of tissues. The mRNA and the protein for SPCA1 were relatively abundant in rat brain, testis and testicular derived cells (myoid cells, germ cells, primary Sertoli cells and TM4 cells; a mouse Sertoli cell line) and epididymal fat pads. Lower levels were found in aorta (rat and porcine), heart, liver, lung and kidney. SPCA activities from a number of tissues were measured and shown to be particularly high in brain, aorta, heart, fat pads and testis. As the proportion of SPCA activity compared to total Ca 2 + ATPase activity in brain, aorta, fat pads and testis were relatively high, this suggests that SPCA1 plays a major role in Ca 2 + storage within these tissues. The subcellular localisation of SPCA1 was shown to be predominantly around the Golgi in both human aortic smooth muscle cells and TM4 cells.