Differential expression patterns of sodium potassium ATPase alpha and beta subunit isoforms in mouse brain during postnatal development (original) (raw)
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Brain Research Bulletin, 1996
We have used isoform-specific antisera against the Na,K-ATPase/]1 (SpETbl) and/~2(AMOG) (SpETb2) subunit isoforms in order to establish their specific cellular and subcellular localization in several developmental stages of the rat central nervous system. Immunocytochemical preparations revealed/~1 isoform protein in most neural cells, being predominantly located in the soma of neurons and astrocytes, with no appreciable developmental variations. In the newborn rat,/~2(AMOG) immunoreactivity was present in cellular processes of astroglia and in the somas of neurons and decreasing in intensity with maturation until adulthood, where no/~2 isoform was detected in neurons. The differential location of these isoforms, both developmentally and at the cellular level suggest a complex regulation of their genes expression and mechanisms of subcellular distribution, as well as functional differences.
Neurons and astroglia express distinct subsets of Na,K-ATPase α and β subunits
Molecular Brain Research, 1994
We have analyzed the expression pattern of Na,K-ATPase a and fl subunit isoforms within the rodent and primate central nervous system. Membrane fractions prepared from rat cerebral cortical type-1 astroeytes and rat cerebellar granule and hippoeampal neurons were characterized by immunoblot analyses using a panel of a and /3 subunit isoform-specific antisera. Each cell type was found to express the al isoform but showed differences in the expression of other subunits. Cortical astroeytes displayed a2 and/32 subunits, whereas cerebellar granule neurons showed expression of a3 and /31 subunits. All three a subunit isotypes were detected in hippocampal neurons. A survey of the immunofluorescent staining pattern of the a3 subunit in rat and monkey brain confirmed that expression of this Na,K-ATPase a subunit isoform was restricted exclusively to neurons. These results suggest that both neurons and astrocytes express multiple, yet distinct, Na,K-ATPase isoenzymes. The identification of cell types expressing limited combinations of a and/3 subunits should provide a framework for understanding the physiological significance of Na,K-ATPase isoenzyme diversity and may provide useful tools for the analysis of cell lineage in the mammalian central nervous system.
Proceedings of the National Academy of Sciences, 1991
We have used in situ hybridization histochemistry to analyze the subceilular distribution of mRNAs encoding Na,K-ATPase a-and /3-subunit isoforms in the rat central nervous system. Substantial differences in the cellspecific pattern ofexpression were found for the genes encoding three isoforms of the a subunit. Transcripts of al-subunit gene were detected in virtually all cell types and structures examined. Expression of a2-subunit mRNA was characteristic of glia, whereas a3-subunit transcripts were predominant in neurons. Transcripts encoding the /31 subunit were detected in neurons, whereas /32-subunit mRNA expression was characteristic of glia. mRNA encoding both /3-subunit isoforms was present in choroidal epithelial cells. The distribution pattern of a-and /8-subunit mRNAs in structures throughout the central nervous system is consistent with the possibility of six structurally distinct Na',K+-ATPase isoenzymes.
Molecular cloning of rat brain Na,K-ATPase alpha-subunit cDNA
Proceedings of the National Academy of Sciences, 1985
We have isolated a cDNA clone for the rat brain Na,K-ATPase a subunit. A Agtll cDNA expression library constructed from mRNA of 1-and 2-week-old rat brains was screened with an antibody reactive with rat brain Na,K-ATPase. A positive phage clone, ArbS, containing a 1200-basepair cDNA insert expressed a fi-galactosidase-cDNA fusion protein that was reactive by immunoblotting with the Na,K-ATPase antibody. This fusion protein was also reactive in ELISA with a monoclonal antibody directed against the a subunit of the Na,K-ATPase. A 27S mRNA species exhibiting sequence hybridization to the cDNA insert of Xrb5 was identified in rat brain, kidney, and liver, as well as in dog kidney. This 27S mRNA exhibited a tissue-specific pattern of abundance consistent with the relative abundance of Na,K-ATPase polypeptides in vivo: kidney > brain > liver. In a ouabainresistant HeLa cell line, C+, which contains minute chromosomes and at least a 10-fold greater number of sodium pumps
Influence of development on Na+/K+-ATPase expression: isoform- and tissue-dependency
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2002
The four isoforms of the catalytic subunit of Na q rK q-ATPase identified in rats differ in their affinities for ions and ouabain. Moreover, its expression is tissue-specific, developmentally and hormonally regulated. The aim of the present work was to evaluate the influence of age on the ratio and density of these isoforms in crude membrane preparations from rat brain hemispheres, brainstem, heart ventricles and kidneys. In all tissues investigated, Na q rK q-ATPase activity was higher in adults than in neonates but brain tissues presented the most remarkable differences. In these tissues, ouabain inhibition curves for Na q rK q-ATPase activity revealed the presence of two processes with different sensitivities to ouabain. An increase of approximately sixfold in the expression of the high affinity isoforms was observed between newborn and adult rats. In contrast, the low affinity isoform increased only approximately twofold in brainstem Ž. whereas it increased ninefold in brain hemispheres. Unlike brain tissues, a decrease almost fourfold in the number of high affinity ouabain binding sites was observed during ontogenesis of the heart. Although limited by the inability to resolve ␣ and ␣ isoforms, present data indicate that the influence of development on the expression of Na q rK q-2 3 ATPase depends not only on the isoform, but also on the tissue where the enzyme is expressed.
Early role for a Na + ,K + -ATPase ( ATP1A3 ) in brain development
Proceedings of the National Academy of Sciences, 2021
Significance By evaluating children with a malformed cerebral cortex, we identified an ATPase pump (ATP1A3) with an early role in brain development. The ATP1A3 pump maintains the physiological concentration of sodium and potassium ions in cells, a process critical for osmotic equilibrium and membrane potential across several developing cell populations. We employed single-cell sequencing approaches to identify key enrichments for ATP1A3 expression during human cortex development. Unravelling this early cell-type–specific pathophysiology in the developing brain offers a potential basis for the treatment of ATP1A3 -related diseases affecting prenatal and early childhood development.