Responses of Ca2+-binding Proteins to Localized, Transient Changes in Intracellular [Ca2+]

Kargacin, Gary J.

doi:10.1006/jtbi.2003.3187

Cited by 12 publications

(8 citation statements)

References 46 publications

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“…The ratio of bound versus free calcium was adjusted to 50 for the vacuole, similar to values reported for the ER of several other cell types (Mogami et al, 1999). This leads to total calcium buffer concentrations of 200 µM in the cytosol and 10 mM in the vacuole, which is similar to previously reported values in other cell types (Briere et al, 2006;Kargacin, 2003;Korngreen et al, 1997). The calcium buffers were implemented using fast-acting mass action kinetics for the cytosol and vacuole such that in the wild type, the reported concentrations are reached:…”

Section: Hypothesis 4: Exchange Of Protons With Vacuolar Calcium Ionssupporting

confidence: 65%

“…The ratio of bound versus free calcium was adjusted to 50 for the vacuole, similar to values reported for the ER of several other cell types (Mogami et al ., 1999). This leads to total calcium buffer concentrations of 200 µ m in the cytosol and 10 m m in the vacuole, which is similar to previously reported values in other cell types (Briere et al ., 2006; Kargacin, 2003; Korngreen et al ., 1997). The calcium buffers were implemented using fast‐acting mass action kinetics for the cytosol and vacuole such that in the wild type, the reported concentrations are reached:

J_{italicCaBuffercyt} = + V_{italiccytoplasm} * false({k 1}_{CaBuffercyt} * (][, {italicCa}_{italiccyt}) * [{italicCaBuffer}_{italiccyt}] false) ‐ {k 2}_{italicCaBuffercyt} * false[{C a_C a B u f f e r}_{cyt} false]

J_{italicCaBuffervac} = + V_{italicvacuole} * false({k 1}_{CaBuffervac} * (][, {italicCa}_{italicvac}) * [{italicCaBuffer}_{italicvac}] false) ‐ {k 2}_{italicCaBuffervac} * false[{C a_C a B u f f e r}_{vac} false]

…”

Section: Modelingmentioning

confidence: 99%

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An integrative view on vacuolar pH homeostasis in Arabidopsis thaliana: Combining mathematical modeling and experimentation

et al. 2021

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The acidification of plant vacuoles is of great importance for various physiological processes, as a multitude of secondary active transporters utilize the proton gradient established across the vacuolar membrane. Vacuolar-type H + -translocating ATPases and a pyrophosphatase are thought to enable vacuoles to accumulate protons against their electrochemical potential. However, recent studies pointed to the ATPase located at the trans-Golgi network/early endosome (TGN/EE) to contribute to vacuolar acidification in a manner not understood as of now. Here, we combined experimental data and computational modeling to test different hypotheses for vacuolar acidification mechanisms. For this, we analyzed different models with respect to their ability to describe existing experimental data. To better differentiate between alternative acidification mechanisms, new experimental data have been generated. By fitting the models to the experimental data, we were able to prioritize the hypothesis in which vesicular trafficking of Ca 2+ ⁄H + -antiporters from the TGN/ EE to the vacuolar membrane and the activity of ATP-dependent Ca 2+ -pumps at the tonoplast might explain the residual acidification observed in Arabidopsis mutants defective in vacuolar proton pump activity. The presented modeling approach provides an integrative perspective on vacuolar pH regulation in Arabidopsis and holds potential to guide further experimental work.

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Section: Hypothesis 4: Exchange Of Protons With Vacuolar Calcium Ionssupporting

confidence: 65%

J_{italicCaBuffercyt} = + V_{italiccytoplasm} * false({k 1}_{CaBuffercyt} * (][, {italicCa}_{italiccyt}) * [{italicCaBuffer}_{italiccyt}] false) ‐ {k 2}_{italicCaBuffercyt} * false[{C a_C a B u f f e r}_{cyt} false]

J_{italicCaBuffervac} = + V_{italicvacuole} * false({k 1}_{CaBuffervac} * (][, {italicCa}_{italicvac}) * [{italicCaBuffer}_{italicvac}] false) ‐ {k 2}_{italicCaBuffervac} * false[{C a_C a B u f f e r}_{vac} false]

…”

Section: Modelingmentioning

confidence: 99%

An integrative view on vacuolar pH homeostasis in Arabidopsis thaliana: Combining mathematical modeling and experimentation

et al. 2021

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“…This sensor may play an essential role in restricted areas of the cell (e.g. subsarcolemma space and dyadic cleft), where the [Ca 2ϩ ] levels can transiently reach 300 -600 M levels within a few milliseconds, when the cell is depolarized (47)(48)(49). On the other hand, the fast CBD1 site is capable of responding to cytosolic [Ca 2ϩ ] changes that take place within the duration of the action potential (10 -200 ms) (Fig.…”

Section: Discussionmentioning

confidence: 99%

Essential Role of the CBD1-CBD2 Linker in Slow Dissociation of Ca2+ from the Regulatory Two-domain Tandem of NCX1

Giladi

Boyman

Mikhasenko

et al. 2010

Journal of Biological Chemistry

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In NCX proteins CBD1 and CBD2 domains are connected through a short linker (3 or 4 amino acids) forming a regulatory tandem (CBD12). Only three of the six CBD12 Ca , whereas the kinetic and equilibrium properties of three Ca 2؉ sites of CBD12-7Ala and CBD1 ؉ CBD2 are similar. Therefore, the linker-dependent interactions in CBD12 decelerate the Ca 2؉ on/off kinetics at a specific CBD1 site by 50 -80-fold, thereby representing Ca 2؉ "occlusion" at CBD12. Notably, the kinetic and equilibrium properties of the remaining two sites of CBD12 are "linker-independent," so their intrinsic properties are preserved in CBD12. In conclusion, the dynamic properties of three sites are specifically modified, conserved, diversified, and integrated by the linker in CBD12, thereby generating a wide range dynamic sensor.The Na ϩ /Ca 2ϩ exchanger proteins (NCX1-3) and their splice variants are expressed in a tissue-specific manner (1-3) and mediate Ca 2ϩ entry/extrusion depending on various factors (4, 5). NCX is "autoregulated" by cytosolic Ca 2ϩ at sites that do not directly participate in the ion translocation (6, 7). For example, the cardiac/neuronal NCX1 variants respond to 0.3-10 M cytosolic Ca 2ϩ , whereas the kidney variant does not (8, 9). Allosteric regulation of NCX involves the interaction of cytosolic Ca 2ϩ with the regulatory loop-f of NCX (10 -14). Although the high affinity regulatory site of NCX1 was discovered 16 years ago (15), only recent studies identified two Ca 2ϩ regulatory domains, CBD1 and CBD2, which form a tandem (CBD12) through a short linker (amino acids 501-504) (16). High resolution x-ray and NMR revealed C 2 -type protein folding in both CBDs (16 -20) that display four Ca 2ϩ sites (Ca1-Ca4) on CBD1 (17,18,20) and two Ca 2ϩ sites (CaI and CaII) on CBD2 (16, 19). The NCX splice variants arise from a combination of 6 small exons (A, B, C, D, E, F), while the splice variant region is exclusively restricted to the CBD2 domain (2-4, 16, 19, 24). Excitable tissues, such as those of the brain (AD splice variant) and heart (ACDEF splice variant) contain exon A, whereas kidney, stomach, and skeletal muscle tissues comprise NCX with exon B (2-5).Equilibrium binding studies have shown that isolated CBD1 protein contains two sites with high affinity for Ca ]-dependent regulation by cytosolic Ca 2ϩ in cellular systems, whereas the primary site of CBD2 (CaI) may contribute to the Ca 2ϩ -dependent relief of Na ϩ -dependent inactivation of intact NCX (23-25). Importantly, the segment that undergoes alternative splicing is located solely within the CBD2 domain, meaning that specific domain-domain interactions may shape the regulatory properties of primary Ca 2ϩ sites at CBD1 (16 -20, 24). Fluorescence resonance energy transfer studies demonstrated that CBD domains of NCX can undergo significant conformational changes in the cell within the excitation-contraction coupling (22,27), although dynamic aspects of relevant conformational transitions, as well as the contribution of each specific Ca 2ϩ site to regulatory even...

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“…Calcium homeostasis has particularly been investigated in vascular SMCs (VSMCs) because of the central role of calcium in the contractile process (Nelson et al, 1990;Fleischmann et al, 1994). Heterogeneous and high local calcium concentrations have been observed in VSMCs in multiple reports (e.g., Deth and van Breemen, 1977;Van Breemen, 1977;van Breemen et al, 1986;Laskey et al, 1992;Kargacin, 1994;Nelson et al, 1995;Rembold et al, 1995), and computer modeling of calcium signaling within the VSMCs showed that high calcium concentrations could occur in restricted spaces and persist for 100-200 ms (Kargacin, 1994(Kargacin, , 2003Naraghi and Neher, 1997). Based in part on these reports, calcium compartmentalization was conceptualized where localized [Ca 2+ ] i could activate the contractile apparatus without altering other calciumdependent pathways (Karaki, 1989).…”

Section: B On the Importance Of Calcium Compartmentalizationmentioning

confidence: 99%

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

et al. 2014

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Responses of Ca2+-binding Proteins to Localized, Transient Changes in Intracellular [Ca2+]

Cited by 12 publications

References 46 publications

An integrative view on vacuolar pH homeostasis in Arabidopsis thaliana: Combining mathematical modeling and experimentation

An integrative view on vacuolar pH homeostasis in Arabidopsis thaliana: Combining mathematical modeling and experimentation

Essential Role of the CBD1-CBD2 Linker in Slow Dissociation of Ca2+ from the Regulatory Two-domain Tandem of NCX1

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

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