The ion channel TRPM7 regulates zinc-depletion-induced MDMX degradation

Wang, Herui; Li, Bin; Asha, Kulsum; Pangilinan, Ryan L; Thuraisamy, Asha; Chopra, Harman; Rokudai, Susumu; Yu, Yong; Prives, Carol; Zhu, Yuyan

doi:10.1016/j.jbc.2021.101292

Cited by 9 publications

(6 citation statements)

References 61 publications

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“…2B and E). A possible explanation was offered by the discovery [48] that MDMX interacts with TRPM7, a bi-functional cation channel protein fused with a kinase domain. TRPM7 is a master regulator of the cellular balance of divalent cations, that mediates the uptake of Zn 2+ , Mg 2+ and Ca 2+ [49], and senses oxidative stress to release Zn 2+ from intracellular vesicles [50].…”

Section: Discussionmentioning

confidence: 99%

“…TRPM7 is a master regulator of the cellular balance of divalent cations, that mediates the uptake of Zn 2+ , Mg 2+ and Ca 2+ [49], and senses oxidative stress to release Zn 2+ from intracellular vesicles [50]. TRPM7 regulates MDMX levels by modulating Zn 2+ concentration, and induces the formation of faster moving forms of MDMX on SDS-PAGE gels [48]. These forms depend on the channel function of TRPM7 and proteasomal degradation.…”

Section: Discussionmentioning

confidence: 99%

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Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Ho,

Chaput,

Sinkey

et al. 2024

Cell Commun Signal

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VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20–150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood–brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10–8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Ho,

Chaput,

Sinkey

et al. 2024

Cell Commun Signal

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“…A study of TRPM7 expression using Zinc (Zn) depletion induced MDMX degradation model showed the direct correlation of TRPM7 modulation and increased tumorigenesis ( Wang et al, 2021 ). Fererra and coworkers in a different study also reported the TRPM2 mediated activation of K + channels in cancer cells responsible for metastatic progression of melanoma ( Ferrera et al, 2021 ).…”

Section: Trp Channels As Potential Drug Targetsmentioning

confidence: 99%

A Review on the Role of TRP Channels and Their Potential as Drug Targets_An Insight Into the TRP Channel Drug Discovery Methodologies

Fallah¹,

Ahuja²,

Lin³

et al. 2022

Front. Pharmacol.

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Transient receptor potential (TRP) proteins are a large group of ion channels that control many physiological functions in our body. These channels are considered potential therapeutic drug targets for various diseases such as neurological disorders, cancers, cardiovascular disease, and many more. The Nobel Prize in Physiology/Medicine in the year 2021 was awarded to two scientists for the discovery of TRP and PIEZO ion channels. Improving our knowledge of technologies for their study is essential. In the present study, we reviewed the role of TRP channel types in the control of normal physiological functions as well as disease conditions. Also, we discussed the current and novel technologies that can be used to study these channels successfully. As such, Flux assays for detecting ionic flux through ion channels are among the core and widely used tools for screening drug compounds. Technologies based on these assays are available in fully automated high throughput set-ups and help detect changes in radiolabeled or non-radiolabeled ionic flux. Aurora’s Ion Channel Reader (ICR), which works based on label-free technology of flux assay, offers sensitive, accurate, and reproducible measurements to perform drug ranking matching with patch-clamp (gold standard) data. The non-radiolabeled trace-based flux assay coupled with the ICR detects changes in various ion types, including potassium, calcium, sodium, and chloride channels, by using appropriate tracer ions. This technology is now considered one of the very successful approaches for analyzing ion channel activity in modern drug discovery. It could be a successful approach for studying various ion channels and transporters, including the different members of the TRP family of ion channels.

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“…For intracellular experiments, the membrane‐permeable and readily available chelator N , N , N′ , N′ ‐tetrakis(2‐pyridinylmethyl)‐1,2‐ethanediamine (TPEN) has been used to chelate mobile zinc in cells, tissues, and live animals [ 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. Given the high affinity of TPEN for zinc(II) ions, with an apparent K d of 0.7 f m , TPEN can chelate zinc ions that are otherwise tightly bound to cellular proteins, leading to programmed cell death by apoptotic pathways [ 79 , 89 , 90 , 91 , 92 ].…”

Section: Chemical Tools To Intercept Mobile Zincmentioning

confidence: 99%

Mobile zinc as a modulator of sensory perception

Goldberg

Lippard

2022

FEBS Letters

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Mobile zinc is an abundant transition metal ion in the central nervous system, with pools of divalent zinc accumulating in regions of the brain engaged in sensory perception and memory formation. Here, we present essential tools that we developed to interrogate the role(s) of mobile zinc in these processes. Most important are (a) fluorescent sensors that report the presence of mobile zinc and (b) fast, Zn‐selective chelating agents for measuring zinc flux in animal tissue and live animals. The results of our studies, conducted in collaboration with neuroscientist experts, are presented for sensory organs involved in hearing, smell, vision, and learning and memory. A general principle emerging from these studies is that the function of mobile zinc in all cases appears to be downregulation of the amplitude of the response following overstimulation of the respective sensory organs. Possible consequences affecting human behavior are presented for future investigations in collaboration with interested behavioral scientists.

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The ion channel TRPM7 regulates zinc-depletion-induced MDMX degradation

Cited by 9 publications

References 61 publications

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

A Review on the Role of TRP Channels and Their Potential as Drug Targets_An Insight Into the TRP Channel Drug Discovery Methodologies

Mobile zinc as a modulator of sensory perception

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