Molecular Dissection of Ca2+ Efflux in Immortalized Proximal Tubule Cells

White, Kenneth E.; Gesek, F. A.; Nesbitt, Teresa; Drezner, Marc K.; Friedman, Peter A.

doi:10.1085/jgp.109.2.217

Cited by 28 publications

(20 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the four plasma membrane Ca 2+ ATPase (PMCA) isoforms, the PMCA1 and PMCA4 isoforms are expressed ubiquitously including in kidney1718. We further investigated whether testosterone-induced SMP30 expression has a role in regulating plasma membrane Ca 2+ ATPase expression.…”

Section: Resultsmentioning

confidence: 99%

Induction of renal senescence marker protein-30 (SMP30) expression by testosterone and its contribution to urinary calcium absorption in male rats

Lin¹,

Jian²,

Chou

et al. 2016

Sci Rep

View full text Add to dashboard Cite

The aim of this study was to investigate the involvement of androgen, mainly testosterone, in the expression of renal senescence marker protein-30 (SMP30) in male rats. We found that the renal SMP30 expression was up-regulated by endogenous testosterone stimulation during puberty. Interestingly, androgen-deficient orchidectomized (ORX) rats exhibited lower SMP30 mRNA and protein expression in the kidney, and that was restored by testosterone propionate (TP) replacement. Abrogation of androgen receptor (AR) activity by co-treatment with flutamide abolished testosterone-induced SMP30 expression in the kidney as well as in the NRK52E cells. However, SMP30 expression was unaltered in the liver of ORX rats. We also showed a positive correlation between renal SMP30 expression and plasma testosterone level during the aging process. TP-induced SMP30 expression in ovariectomized (OVX) rats was observed and was an evidence to explain the gender difference of SMP30 levels. Immunofluorescence assay showed that renal SMP30 was specifically expressed in the proximal tubular segments of the kidney. The urinary Ca2+ level was increased in both ORX and male aging rats. Taken together, our results indicate a novel role of testosterone in regulating SMP30 expression specifically in the kidney to contribute to urinary calcium absorption.

show abstract

Section: Resultsmentioning

confidence: 99%

Induction of renal senescence marker protein-30 (SMP30) expression by testosterone and its contribution to urinary calcium absorption in male rats

Lin¹,

Jian²,

Chou

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…For RT–PCR analysis of PMCA isoforms, two different sets of primers were used, those described by Reisner et al . (1997) and by White et al . (1997).…”

Section: Methodsmentioning

confidence: 99%

“…mRNA was extracted from brain samples or isolated pancreatic acini with a mRNA extraction kit as per the kit instructions. For RT±PCR analysis of PMCA isoforms, two different sets of primers were used, those described by Reisner et al (1997) and by White et al (1997). For RT±PCR analysis of Syts, the following primers were used: Syt I, sense 5¢-GTGCCA-TACTCGGAATTAGGTG-3¢, antisense 5¢-GCTGAAGGACTCATT-GTAGTAGGG-3¢ (393 bp); Syt II, sense 5¢-ACACTGACGAGATCC-ATAGCTATC-3¢, antisense 5¢-GCACATACAGGTGTACACACA-CAC-3¢ (402 bp); Syt III, sense 5¢-GTACCTCTATGGTTCTGACCA-GCTC-3¢, antisense 5¢-GGAGGTAGCAGAGAGAGAAGTTGAG-3¢ (404 bp); Syt IV, sense 5¢-GAGAAGAAGCACAGAGTGAAGACC-3¢, antisense 5¢-GGTACAGGTTCACTTTGACGTAGG-3¢ (397 bp); and bactin, sense 5¢-TGTTACCAACTGGGACGACA-3¢, antisense 5¢-TCT-CAGCTGTGGTGGTGAAG-3¢ (392 bp).…”

Section: Rt±pcr Analysismentioning

confidence: 99%

Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2+/- mice

et al. 2001

View full text Add to dashboard Cite

Shin contributed equally to this workDarier's disease (DD) is a high penetrance, autosomal dominant mutation in the ATP2A2 gene, which encodes the SERCA2 Ca 2+ pump. Here we have used a mouse model of DD, a SERCA2 +/± mouse, to de®ne the adaptation of Ca 2+ signaling and Ca 2+ -dependent exocytosis to a deletion of one copy of the SERCA2 gene. The [Ca 2+ ] i transient evoked by maximal agonist stimulation was shorter in cells from SERCA2 +/± mice, due to an up-regulation of speci®c plasma membrane Ca 2+ pump isoforms. The change in cellular Ca 2+ handling caused~50% reduction in [Ca 2+ ] i oscillation frequency. Nonetheless, agonist-stimulated exocytosis was identical in cells from wild-type and SERCA2 +/± mice. This was due to adaptation in the levels of the Ca 2+ sensors for exocytosis synaptotagmins I and III in cells from SERCA2 +/± mice. Accordingly, exocytosis was~10-fold more sensitive to Ca 2+ in cells from SERCA2 +/± mice. These ®ndings reveal a remarkable plasticity and adaptability of Ca 2+ signaling and Ca 2+ -dependent cellular functions in vivo, and can explain the normal function of most physiological systems in DD patients.

show abstract

“…For example, the sensitivity of the RT-PCR approach may be responsible for the detection in some tissues of alternative splice products of PMCAs 1 and 4 at splice site B (87) and may have led to an overestimate of the diversity of alternative splice options utilized in some cell types (74). The importance of a careful analysis of all RT-PCR products by nucleotide sequencing and the inadequacy of agarose gel electrophoresis and Southern blotting alone to determine alternative splice variants have been pointed out by Zacharias et al (185) and White et al (180). Information concerning the exact cellular distribution of the various splice variants is generally not obtainable by RT-PCR because all tissue structure and cellular identity is destroyed in the process of extracting the RNA.…”

Section: Rt-pcrmentioning

confidence: 99%

Role of Alternative Splicing in Generating Isoform Diversity Among Plasma Membrane Calcium Pumps

Strehler

Zacharias

2001

Physiological Reviews

535

512

View full text Add to dashboard Cite

Calcium pumps of the plasma membrane (also known as plasma membrane Ca(2+)-ATPases or PMCAs) are responsible for the expulsion of Ca(2+) from the cytosol of all eukaryotic cells. Together with Na(+)/Ca(2+) exchangers, they are the major plasma membrane transport system responsible for the long-term regulation of the resting intracellular Ca(2+) concentration. Like the Ca(2+) pumps of the sarco/endoplasmic reticulum (SERCAs), which pump Ca(2+) from the cytosol into the endoplasmic reticulum, the PMCAs belong to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. Mammalian PMCAs are encoded by four separate genes, and additional isoform variants are generated via alternative RNA splicing of the primary gene transcripts. The expression of different PMCA isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. PMCAs 1 and 4 are found in virtually all tissues in the adult, whereas PMCAs 2 and 3 are primarily expressed in excitable cells of the nervous system and muscles. During mouse embryonic development, PMCA1 is ubiquitously detected from the earliest time points, and all isoforms show spatially overlapping but distinct expression patterns with dynamic temporal changes occurring during late fetal development. Alternative splicing affects two major locations in the plasma membrane Ca(2+) pump protein: the first intracellular loop and the COOH-terminal tail. These two regions correspond to major regulatory domains of the pumps. In the first cytosolic loop, the affected region is embedded between a putative G protein binding sequence and the site of phospholipid sensitivity, and in the COOH-terminal tail, splicing affects pump regulation by calmodulin, phosphorylation, and differential interaction with PDZ domain-containing anchoring and signaling proteins. Recent evidence demonstrating differential distribution, dynamic regulation of expression, and major functional differences between alternative splice variants suggests that these transporters play a more dynamic role than hitherto assumed in the spatial and temporal control of Ca(2+) signaling. The identification of mice carrying PMCA mutations that lead to diseases such as hearing loss and ataxia, as well as the corresponding phenotypes of genetically engineered PMCA "knockout" mice further support the concept of specific, nonredundant roles for each Ca(2+) pump isoform in cellular Ca(2+) regulation.

show abstract

Molecular Dissection of Ca2+ Efflux in Immortalized Proximal Tubule Cells

Cited by 28 publications

References 60 publications

Induction of renal senescence marker protein-30 (SMP30) expression by testosterone and its contribution to urinary calcium absorption in male rats

Induction of renal senescence marker protein-30 (SMP30) expression by testosterone and its contribution to urinary calcium absorption in male rats

Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2+/- mice

Role of Alternative Splicing in Generating Isoform Diversity Among Plasma Membrane Calcium Pumps

Contact Info

Product

Resources

About