The plasma membrane Ca2+ ATPase of animal cells: Structure, function and regulation

Leva, Francesca Di; Domi, Teuta; Fedrizzi, Laura; Lim, Dmitry; Carafoli, Ernesto

doi:10.1016/j.abb.2008.02.026

Cited by 233 publications

(200 citation statements)

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“…13,14 However, it has been difficult to speculate the exact role of ATP2B1 in physiology because of the large number of isoforms and the multiplicity of interacting molecules. 15 Related to its role in blood pressure, it is not clear yet whether ATP2B1 directly regulates the contraction and dilation of vascular smooth muscle by pumping out intracellular Ca ++ or it indirectly regulates the blood pressure by transmitting signals from vascular endothelial cells into the vascular smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Recapitulation of two genomewide association studies on blood pressure and essential hypertension in the Korean population

et al. 2010

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Essential hypertension causes high rates of morbidity and mortality, primarily due to its complications, and its development is regulated by genetic risk and environmental factors. However, until recent genomewide association studies (GWASs) were reported, the genetic factors were unknown. Two GWASs on systolic blood pressure (SBP), diastolic blood pressure (DBP) and hypertension in Caucasians-Global Blood Pressure Genetics (Global BPgen) and Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE)-reported 51 single-nucleotide polymorphisms (SNPs) in 12 loci at Po4Â10 À7 . Because the prevalence, age of onset and severity of complications of hypertension vary between ethnic groups, we wanted to investigate these results in other ethnic groups. We examined the association of 27 of the 51 SNPs in 8512 unrelated individuals from Korean Association REsource (KARE), a GWAS that was based on epidemiological cohorts in Korea. Four loci-ATP2B1 (ATPase, Ca ++ transporting, plasma membrane 1), CSK (c-src tyrosine kinase), CYP17A1 (cytochrome P450 17A1) and PLEKHA7 (pleckstrin homology domain-containing family A member 7)-were associated with blood pressure and hypertension in the Korean population.

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Section: Discussionmentioning

confidence: 99%

Recapitulation of two genomewide association studies on blood pressure and essential hypertension in the Korean population

et al. 2010

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“…Gln-talin is the Ct fragment of talin, an adaptor protein that interacts with the integrin family of cell adhesion transmembrane proteins. 139,154,155 #13. Leu-NF2 is the Ct fragment of NF2 (merlin), a tumor suppressor and cytoskeletal protein.…”

Section: Monitoring Protein Fragments and Reacting To Their Accumulationmentioning

confidence: 99%

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

Varshavsky

2012

Protein Science

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Despite extensive understanding of sleep regulation, the molecular-level cause and function of sleep are unknown. I suggest that they originate in individual neurons and stem from increased production of protein fragments during wakefulness. These fragments are transient parts of protein complexes in which the fragments were generated. Neuronal Ca 21 fluxes are higher during wakefulness than during sleep. Subunits of transmembrane channels and other proteins are cleaved by Ca 21 -activated calpains and by other nonprocessive proteases, including caspases and secretases. In the proposed concept, termed the fragment generation (FG) hypothesis, sleep is a state during which the production of fragments is decreased (owing to lower Ca 21 transients) while fragment-destroying pathways are upregulated. These changes facilitate the elimination of fragments and the remodeling of protein complexes in which the fragments resided. The FG hypothesis posits that a proteolytic cleavage, which produces two fragments, can have both deleterious effects and fitness-increasing functions. This (previously not considered) dichotomy can explain both the conservation of cleavage sites in proteins and the evolutionary persistence of sleep, because sleep would counteract deleterious aspects of protein fragments. The FG hypothesis leads to new explanations of sleep phenomena, including a longer sleep after sleep deprivation. Studies in the 1970s showed that ethanol-induced sleep in mice can be strikingly prolonged by intracerebroventricular injections of either Ca 21 alone or Ca 21 and its ionophore (Erickson et al., Science 1978;199:1219-1221 Harris, Pharmacol Biochem Behav 1979;10:527-534; Erickson et al., Pharmacol Biochem Behav 1980;12:651-656). These results, which were never interpreted in connection to protein fragments or the function of sleep, may be accounted for by the FG hypothesis about molecular causation of sleep.

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“…ATP2B1 gene encodes PMCA1 protein). Numerous splice variants of each gene have been found to be functionally expressed, with the possibility that over 30 variants can be generated (Keeton et al, 1993;Di Leva et al, 2008). The N and C termini of PMCA are both intracellular, with the far longer C terminus containing regulatory domain binding sites and PDZ domains physically linking to interacting partners (James et al, 1988;Kessler et al, 1992;Hofmann et al, 1993;Di Leva et al, 2008).…”

Section: Plasma Membrane Calcium Atpasesmentioning

confidence: 99%

“…The N and C termini of PMCA are both intracellular, with the far longer C terminus containing regulatory domain binding sites and PDZ domains physically linking to interacting partners (James et al, 1988;Kessler et al, 1992;Hofmann et al, 1993;Di Leva et al, 2008). Extracellular loops are believed to be of minimal length (Di Leva et al, 2008), Fig. 2.…”

Section: Plasma Membrane Calcium Atpasesmentioning

confidence: 99%

Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension

Little

Cartwright

Neyses

et al. 2016

Pharmacology & Therapeutics

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The incidence of hypertension, the major modifiable risk factor for cardiovascular disease, is increasing. Thus, there is a pressing need for the development of new and more effective strategies to prevent and treat hypertension. Development of these relies on a continued evolution of our understanding of the mechanisms which control blood pressure (BP). Resistance arteries are important in the regulation of total peripheral resistance and BP; changes in their structure and function are strongly associated with hypertension. Anti-hypertensives which both reduce BP and reverse changes in resistance arterial structure reduce cardiovascular risk more than therapies which reduce BP alone. Hence, identification of novel potential vascular targets which modify BP is important. Hypertension is a multifactorial disorder which may include a genetic component. Genome wide association studies have identified ATP2B1, encoding the calcium pump plasma membrane calcium ATPase 1 (PMCA1), as having a strong association with BP and hypertension. Knockdown or reduced PMCA1 expression in mice has confirmed a physiological role for PMCA1 in BP and resistance arterial regulation. Altered expression or inhibition of PMCA4 has also been shown to modulate these parameters. The mechanisms whereby PMCA1 and 4 can modulate vascular function remain to be fully elucidated but may involve regulation of intracellular calcium homeostasis and/or comprise a structural role. However, clear physiological links between PMCA and BP, coupled with experimental studies directly linking PMCA1 and 4 to changes in BP and arterial function, suggest that they may be important targets for the development of new pharmacological modulators of BP.

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The plasma membrane Ca2+ ATPase of animal cells: Structure, function and regulation

Cited by 233 publications

References 100 publications

Recapitulation of two genomewide association studies on blood pressure and essential hypertension in the Korean population

Recapitulation of two genomewide association studies on blood pressure and essential hypertension in the Korean population

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension

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