Structural mechanism of cooperative regulation of calcium-sensing receptor-mediated cellular signaling

Deng, Xiaonan; Yao, Xin; Miller, Cassandra; Hamelberg, Donald; Kirberger, Michael; Moremen, Kelley W.; Hu, Jian; Yang, Jenny J.

doi:10.1016/j.cophys.2020.08.020

Cited by 11 publications

(10 citation statements)

References 54 publications

(73 reference statements)

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“…Importantly,TNCA (500 mM) was able to reverse the effect of E297K mutation on both sensitivity (3.10 AE 0.13 mM, N = 20, p < 0.0001) and cooperativity (Hill coefficient:3 .08 AE 0.40 with TNCA vs.2 .12 AE 0.18 without TNCA), supporting co-activation working model (Figures 6C-E and Figures S19J,K). [35][36] In addition, R-CatchER was able to detect ER Ca 2+ oscillations triggered by 1.0 mM extracellular Ca 2+ and 10 mMo ft he CaSR allosteric activator Cinacalcet in ahuman medullary Ccell carcinoma cell line TT,with wider and lower frequent peaks (Figure 6F).…”

Section: Methodsmentioning

confidence: 96%

Tuning Protein Dynamics to Sense Rapid Endoplasmic‐Reticulum Calcium Dynamics

et al. 2021

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Multi-scale calcium (Ca 2+ )d ynamics,e xhibiting wide-ranging temporal kinetics,constitutes aubiquitous mode of signal transduction. We report an ovel endoplasmicreticulum (ER)-targeted Ca 2+ indicator,R -CatchER,w hich showed superior kinetics in vitro (k off ! 2 10 3 s À1 ,k on ! 7 10 6 M À1 s À1 )a nd in multiple cell types.R -CatchER captured spatiotemporal ER Ca 2+ dynamics in neurons and hotspots at dendritic branchpoints,e nabled the first report of ER Ca 2+ oscillations mediated by calcium sensing receptors (CaSRs), and revealed ER Ca 2+ -based functional cooperativity of CaSR. We elucidate the mechanism of R-CatchER and propose ap rinciple to rationally design genetically encoded Ca 2+ indicators with as ingle Ca 2+ -binding site and fast kinetics by tuning rapid fluorescent-protein dynamics and the electrostatic potential around the chromophore.T he design principle is supported by the development of G-CatchER2, an upgrade of our previous (G-)CatchER with improved dynamic range.Our work may facilitate protein design, visualizing Ca 2+ dynamics, and drug discovery.

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Section: Methodsmentioning

confidence: 96%

Tuning Protein Dynamics to Sense Rapid Endoplasmic‐Reticulum Calcium Dynamics

et al. 2021

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“…The first one is pyrrolizidine alkaloids, found in both Palaui and Laiban honey. The compound lycoperodine-1 (Table S1) is considered an agonist of Ca 2+ sensing receptors (CaSR) implicated in many diseases [42]. Equally important is the reversible transformation of pyrrolizidine alkaloids to the more hydrophobic N-oxide form [43].…”

Section: Resultsmentioning

confidence: 99%

Multi-omics Based Chemical Ecology of Philippine Forest Honey highlights endangered Pterocarpus indicus Willd. tree and important community-driven conservation efforts

Molino,

Weerd,

Torreno

et al. 2023

Preprint

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Cooperation among Filipino scientists, conservationists, and forest-based communities paved the way for the chemical ecology investigation of Apis breviligula Maa., Apis cerana Fabr., and Tetragonula biroi (Friese) in priority forest landscapes of the Sierra Madre Mountain Range. The Philippine National Tree and unfortunately endangered Pterocarpus indicus Willd (loc. Narra) proved to be important, especially in Palaui Island where honey from A. cerana is close to being monofloral. Aside from P. indicus and its small molecule marker hypaphorine, caffeine was detected in Palaui honey beautifully reflecting the way of life of native Agtas who manage a small coffee plantation. The abundance of caffeine, however, is higher in stingless honey samples from Tanay, Rizal where Coffea trees have been extensively included in restoration activities over the past few decades. Our results imply the possibility of using honey as an ecological monitoring tool while generating baseline chemical information that reflects the state of Philippine forests. Furthermore, the identification of unique chemical components in forest honey can be further used in programs that assist indigenous communities in safeguarding the ownership and origin of forest honey sources.

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“…The present study showed an identical result. The binding sites of extracellular Ca 2+ in hCaSR are five extracellular domain regions 31 . In cCaSR, only one amino acid (Ser-388) in Site 4 was mutated to Thr among these important sites.…”

Section: Discussionmentioning

confidence: 99%

Oral expressions and functional analyses of the extracellular calcium-sensing receptor (CaSR) in chicken

Omori

Kawabata

Yoshida

et al. 2022

Sci Rep

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In vertebrates, the extracellular calcium-sensing receptor (CaSR) plays a key role in calcium homeostasis by sensing slight changes in extracellular Ca2+. CaSR is also expressed in mammals including rodent taste cells and is involved in sensing kokumi, a rich, savory quality that enhances the intensities of salty, sweet, and umami tastes. In this study, we focused on chicken CaSR (cCaSR) since calcium is an essential nutrient that is necessary for making eggshell and for the extremely rapid initial growth of bones. First we confirmed that cCaSR is expressed in taste cells. Next we cloned the cCaSR gene from kidney and transiently transfected human embryonic kidney 293 T (HEK293T) cells with the recombinant cCaSR, or empty vector and looked for the agonists and allosteric modulators (including kokumi substances) of cCaSR by Ca2+ imaging. We found that cCaSR was activated by extracellular Ca2+ and Mg2+ in a dose dependent manner. Several L-amino acids and kokumi substances such as glutathione enhanced the response of cCaSR. In addition, NPS2143 as a negative allosteric modulator of human CaSR negatively modulated the response of cCaSR. These results suggest that cCaSR can sense extracellular Ca2+ and Mg2+ as well as positive and negative allosteric modulators. Taken together, the results imply that CaSR might be a multifunctional receptor for calcium, amino acids, and kokumi substances in chicken. The present finding that functional CaSR is expressed in the chicken oral tissues will allow us to further elucidate the physiological role of CaSR in the chickens' taste sense, and to create new feeds that will contribute to the poultry industry.

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Structural mechanism of cooperative regulation of calcium-sensing receptor-mediated cellular signaling

Cited by 11 publications

References 54 publications

Tuning Protein Dynamics to Sense Rapid Endoplasmic‐Reticulum Calcium Dynamics

Tuning Protein Dynamics to Sense Rapid Endoplasmic‐Reticulum Calcium Dynamics

Multi-omics Based Chemical Ecology of Philippine Forest Honey highlights endangered Pterocarpus indicus Willd. tree and important community-driven conservation efforts

Oral expressions and functional analyses of the extracellular calcium-sensing receptor (CaSR) in chicken

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