Plasma membrane calcium ATPases and related disorders

Giacomello, Marta; Mario, Agnese De; Scarlatti, Chiara; Primerano, Simona; Carafoli, Ernesto

doi:10.1016/j.biocel.2012.09.016

Cited by 30 publications

(28 citation statements)

References 77 publications

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“…The PMCA family is part of the superfamily of P-type ATPase pumps that form a stable phosphorylated intermediate as it hydrolyzes one molecule of ATP for each Ca 2+ transported (Strehler and Zacharias, 2001; Cai and Lytton, 2004). The phosphorylated enzyme intermediate of the P-type ATPases, which include the SERCA family of transporters in the ER membrane (Giacomello et al, 2013), occurs between γ-phosphate of a hydrolyzed ATP with a D-residue in a highly conserved region of the ATPase pump (Brini and Carafoli, 2011). …”

Section: Introductionmentioning

confidence: 99%

“…Its expression is highest in the nervous system, heart, skeletal muscle, and intestine (Zacharias and Kappen, 1999), and regulated by growth factors such as glucocorticoids and Vitamin D (Zacharias and Kappen, 1999; Giacomello et al, 2013). PMCA2 is expressed mainly in the brain, heart, mammary glands and ear, and decreased expression of PMCA2 causes increased apoptosis in breast cancer cells (Curry et al, 2012; Giacomello et al, 2013). PMCA3 has the highest calmodulin affinity and is detected primarily in the brain and skeletal muscles (Krebs, 2009; Giacomello et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…PMCA2 is expressed mainly in the brain, heart, mammary glands and ear, and decreased expression of PMCA2 causes increased apoptosis in breast cancer cells (Curry et al, 2012; Giacomello et al, 2013). PMCA3 has the highest calmodulin affinity and is detected primarily in the brain and skeletal muscles (Krebs, 2009; Giacomello et al, 2013). PMCA4 is involved in the fertilization process and cardiac function, and has been found to associate with lipid rafts, which often function to aggregate protein complexes important in signaling pathways (Giacomello et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…PMCA3 has the highest calmodulin affinity and is detected primarily in the brain and skeletal muscles (Krebs, 2009; Giacomello et al, 2013). PMCA4 is involved in the fertilization process and cardiac function, and has been found to associate with lipid rafts, which often function to aggregate protein complexes important in signaling pathways (Giacomello et al, 2013). It has been suggested that PMCA4 is more involved in cell-specific Ca 2+ signaling than as a pump for bulk Ca 2+ export (Strehler, 2013; Brini et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Multiple Calcium Export Exchangers and Pumps Are a Prominent Feature of Enamel Organ Cells

et al. 2017

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Calcium export is a key function for the enamel organ during all stages of amelogenesis. Expression of a number of ATPase calcium transporting, plasma membrane genes (ATP2B1-4/PMCA1-4), solute carrier SLC8A genes (sodium/calcium exchanger or NCX1-3), and SLC24A gene family members (sodium/potassium/calcium exchanger or NCKX1-6) have been investigated in the developing enamel organ in earlier studies. This paper reviews the calcium export pathways that have been described and adds novel insights to the spatiotemporal expression patterns of PMCA1, PMCA4, and NCKX3 during amelogenesis. New data are presented to show the mRNA expression profiles for the four Atp2b1-4 gene family members (PMCA1-4) in secretory-stage and maturation-stage rat enamel organs. These data are compared to expression profiles for all Slc8a and Slc24a gene family members. PMCA1, PMCA4, and NCKX3 immunolocalization data is also presented. Gene expression profiles quantitated by real time PCR show that: (1) PMCA1, 3, and 4, and NCKX3 are most highly expressed during secretory-stage amelogenesis; (2) NCX1 and 3, and NCKX6 are expressed during secretory and maturation stages; (3) NCKX4 is most highly expressed during maturation-stage amelogenesis; and (4) expression levels of PMCA2, NCX2, NCKX1, NCKX2, and NCKX5 are negligible throughout amelogenesis. In the enamel organ PMCA1 localizes to the basolateral membrane of both secretory and maturation ameloblasts; PMCA4 expression is seen in the basolateral membrane of secretory and maturation ameloblasts, and also cells of the stratum intermedium and papillary layer; while NCKX3 expression is limited to Tomes' processes, and the apical membrane of maturation-stage ameloblasts. These new findings are discussed in the perspective of data already present in the literature, and highlight the multiplicity of calcium export systems in the enamel organ needed to regulate biomineralization.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Multiple Calcium Export Exchangers and Pumps Are a Prominent Feature of Enamel Organ Cells

et al. 2017

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“…Among the 4 different PMCA genes PMCA2 has the highest binding affinity for calmodulin, but also a very high basal Ca 2+ activity in the absence of calmodulin [71] which could be important in specialized cells where a continuous Ca 2+ pumping activity at high rate is demanded. Splicing at site A inserts up to 3 exons, at site C one or two exons (see Fig.…”

Section: Pmca2mentioning

confidence: 99%

The plethora of PMCA isoforms: Alternative splicing and differential expression

Krebs

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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PMCA4 (ATP2B4) mutation in familial spastic paraplegia causes delay in intracellular calcium extrusion

Pang

et al. 2015

Brain and Behavior

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BackgroundFamilial spastic paraplegia (FSP) is a heterogeneous group of disorders characterized primarily by progressive lower limb spasticity and weakness. More than 50 disease loci have been described with different modes of inheritance. Recently, we described a novel missense mutation (c.803G>A, p.R268Q) in the plasma membrane calcium ATPase (PMCA4, or ATP2B4) gene in a Chinese family with autosomal dominant FSP. Further to this finding, here we describe the functional effect of this mutation.MethodsAs PMCA4 removes cytosolic calcium, we measured transient changes and the time-dependent decay of cytosolic calcium level as visualized by using fura-2 fluorescent dye with confocal microscopy in human SH-SY5Y neuroblastoma cells overexpressing either wild-type or R268Q mutant PMCA4.ResultsOverexpressing both wild-type and R268Q PMCA4 significantly reduced maximum calcium surge after KCl-induced depolarization as compared with vector control cells. However, cells overexpressing mutant PMCA4 protein demonstrated significantly higher level of calcium surge when compared with wild-type. Furthermore, the steady-state cytosolic calcium concentration in these mutant cells remained markedly higher than the wild-type after SERCA inhibition by thapsigargin.ConclusionOur result showed that p.R268Q mutation in PMCA4 resulted in functional changes in calcium homeostasis in human neuronal cells. This suggests that calcium dysregulation may be associated with the pathogenesis of FSP.

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Plasma membrane calcium ATPases and related disorders

Cited by 30 publications

References 77 publications

Multiple Calcium Export Exchangers and Pumps Are a Prominent Feature of Enamel Organ Cells

Multiple Calcium Export Exchangers and Pumps Are a Prominent Feature of Enamel Organ Cells

The plethora of PMCA isoforms: Alternative splicing and differential expression

PMCA4 (ATP2B4) mutation in familial spastic paraplegia causes delay in intracellular calcium extrusion

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