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Günther, Gitta; Huschke, Wolfram; Steiner, Walter

doi:10.1007/978-3-476-02958-4_20

Cited by 7 publications

(9 citation statements)

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“…The specificity of this mechanism, however, is far from defined. Different cations including Ca 2+ or Mn 2+ , or anions such as HCO 3 − , Cl − , or choline, [147,148] have been reported to be utilized by this mechanism to extrude Mg 2+ . Hence, it remains unclear whether we are in the presence of distinct transport mechanisms, or in the presence of a transporter that can operate as an antiporter for cations or a sinporter for cations and anions based upon the experimental conditions.…”

Section: Mg2+ Transport Mechanismsmentioning

confidence: 99%

Cellular magnesium homeostasis

Romani

2011

Archives of Biochemistry and Biophysics

440

425

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Magnesium, the second most abundant cellular cation after potassium, is essential to regulate numerous cellular functions and enzymes, including ion channels, metabolic cycles, and signaling pathways, as attested by more than 1000 entries in the literature. Despite significant recent progress, however, our understanding of how cells regulate Mg2+ homeostasis and transport still remains incomplete. For example, the occurrence of major fluxes of Mg2+ in either direction across the plasma membrane of mammalian cells following metabolic or hormonal stimuli has been extensively documented. Yet, the mechanisms ultimately responsible for magnesium extrusion across the cell membrane have not been cloned. Even less is known about the regulation in cellular organelles. The present review is aimed at providing the reader with a comprehensive and up-to-date understanding of the mechanisms enacted by eukaryotic cells to regulate cellular Mg2+ homeostasis and how these mechanisms are altered under specific pathological conditions.

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Section: Mg2+ Transport Mechanismsmentioning

confidence: 99%

Cellular magnesium homeostasis

Romani

2011

Archives of Biochemistry and Biophysics

440

425

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“…Equally contradictory are the findings of variable Na ϩ / Mg 2ϩ stoichiometries (1,19), the role of trans-membrane potential, and the partial and variable effectiveness of inhibitors such as amiloride (for review see Refs. 1,5,18,and 20). In principle, these discrepancies could be accounted for by the co-existence of separate plasma membrane Mg 2ϩ transporters each operating with different mechanisms and sensitivity to inhibitors.…”

mentioning

confidence: 99%

“…Yet, the Mg 2ϩ transporter(s) has not been isolated, and even the basic kinetic properties of Mg 2ϩ cellular transport remain confusing and contradictory. For example, the dependence of Mg 2ϩ release on extracellular Na ϩ has been established in invertebrate and mammalian cells (11-16) but Na ϩ -independent pathways have also been reported (1,8,9,17,18). Equally contradictory are the findings of variable Na ϩ / Mg 2ϩ stoichiometries (1,19), the role of trans-membrane potential, and the partial and variable effectiveness of inhibitors such as amiloride (for review see Refs.…”

mentioning

confidence: 99%

Differential Localization and Operation of Distinct Mg2+ Transporters in Apical and Basolateral Sides of Rat Liver Plasma Membrane

Cefaratti

Romani

Scarpa³

2000

Journal of Biological Chemistry

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Upon activation of specific cell signaling, hepatocytes rapidly accumulate or release an amount of Mg 2؉ equivalent to 10% of their total Mg 2؉ content. Although it is widely accepted that Mg 2؉ efflux is Na ؉ -dependent, little is known about transporter identity and the overall regulation. Even less is known about the mechanism of cellular Mg 2؉ uptake. Using sealed and right-sided rat liver plasma membrane vesicles representing either the basolateral (bLPM) or apical (aLPM) domain, it was possible to dissect three different Mg 2؉ transport mechanisms based upon specific inhibition, localization within the plasma membrane, and directionality. The bLPM possesses only one Mg 2؉ transporter, which is strictly Na ؉ -dependent, bi-directional, and not inhibited by amiloride. The aLPM possesses two separate Mg 2؉ transporters. One, similar to that in the bLPM because it strictly depends on Na ؉ transport, and it can be differentiated from that of the bLPM because it is unidirectional and fully inhibited by amiloride. The second is a novel Ca 2؉ /Mg 2؉ exchanger that is unidirectional and inhibited by amiloride and imipramine. Hence, the bLPM transporter may be responsible for the exchange of Mg 2؉ between hepatocytes and plasma, and vice versa, shown in livers upon specific metabolic stimulation, whereas the aLPM transporters can only extrude Mg 2؉ into the biliary tract. The dissection of these three distinct pathways and, therefore, the opportunity to study each individually will greatly facilitate further characterization of these transporters and a better understanding of Mg 2؉ homeostasis.Magnesium, the second most abundant cation within mammalian cells, is necessary for a variety of metabolic and cellular functions (1-5). Under resting conditions, cellular-free Mg 2ϩ concentration is held at 0.5-0.8 mM, well below its predicted electrochemical equilibrium, and approximately 5 mM Mg 2ϩ is complexed with ATP and other metabolites (1, 5). In several tissues such as heart and liver, specific hormonal or metabolic stimulation causes, within a few minutes, a massive mobilization of cellular Mg 2ϩ (6 -9). Although cytosolic-free Mg 2ϩ undergoes minimal changes, several intracellular signals leading to a cAMP increase induce a loss of 5-10% of total cellular Mg 2ϩ (6 -9). Conversely, signals activating protein kinase C result in an accumulation of Mg 2ϩ and a consequent increase of total cellular Mg 2ϩ by 5-10% (10). These findings underscore the operation of a very powerful Mg 2ϩ transport machinery within the plasma membranes of mammalian cells. Yet, the Mg 2ϩ transporter(s) has not been isolated, and even the basic kinetic properties of Mg 2ϩ cellular transport remain confusing and contradictory. For example, the dependence of Mg 2ϩ release on extracellular Na ϩ has been established in invertebrate and mammalian cells (11-16) but Na ϩ -independent pathways have also been reported (1,8,9,17,18). Equally contradictory are the findings of variable Na ϩ / Mg 2ϩ stoichiometries (1,19), the role of trans-membrane potenti...

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“…dependent, which has led to varying estimates of the free Mg 2+ concentration ranging between 0.5 mM and 2 mM. [72] What sometimes seems forgotten, however, is that a large fraction of the total ≈20 mM Mg 2+ in the cell is bound by nucleic acids, especially RNA, since ≈90% of the negatively charged phosphates are charge-neutralized by Mg 2+ ; [73] similarly, each NTP typically chelates one Mg 2+ ion. [74] Given its rapid dissociation rate constant, the divalent ion therefore will quickly equilibrate between many Mg 2+ -binding sites in the cell (Figure 3) so that a chelating detection probe is subject to competition for binding of Mg 2+ , especially from those competitors with a higher affinity for Mg 2+ or a higher concentration than the probe itself ( Figure 2).…”

Section: Biological Specificity Refined By Diverse Cellular Interactmentioning

confidence: 99%

Biological Pathway Specificity in the Cell—Does Molecular Diversity Matter?

Walter

2019

BioEssays

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Biology arises from the crowded molecular environment of the cell, rendering it a challenge to understand biological pathways based on the reductionist, low‐concentration in vitro conditions generally employed for mechanistic studies. Recent evidence suggests that low‐affinity interactions between cellular biopolymers abound, with still poorly defined effects on the complex interaction networks that lead to the emergent properties and plasticity of life. Mass‐action considerations are used here to underscore that the sheer number of weak interactions expected from the complex mixture of cellular components significantly shapes biological pathway specificity. In particular, on‐pathway—i.e., “functional”—become those interactions thermodynamically and kinetically stable enough to survive the incessant onslaught of the many off‐pathway (“nonfunctional”) interactions. Consequently, to better understand the molecular biology of the cell a further paradigm shift is needed toward mechanistic experimental and computational approaches that probe intracellular diversity and complexity more directly. Also see the video abstract here https://youtu.be/T19X_zYaBzg.

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T

Cited by 7 publications

References 0 publications

Cellular magnesium homeostasis

Cellular magnesium homeostasis

Differential Localization and Operation of Distinct Mg2+ Transporters in Apical and Basolateral Sides of Rat Liver Plasma Membrane

Biological Pathway Specificity in the Cell—Does Molecular Diversity Matter?

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