The crucial role of the TRPM7 kinase domain in the early stage of amelogenesis

Ogata, Kayoko; Tsumuraya, Tomoyuki; Oka, Kyoko; Shin, Masashi; Okamoto, Fujio; Kajiya, Hiroshi; Katagiri, Chiaki; Ozaki, Masao; Matsushita, Masayuki; Okabe, Koji

doi:10.1038/s41598-017-18291-0

Cited by 16 publications

(20 citation statements)

References 39 publications

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“…We used in situ hybridization (ISH) to verify the efficient mutagenesis of Trpm7 . In line with other studies ( 39 – 41 ), we observed that in control kidneys, Trpm7 was abundantly expressed in tubule segments characterized by apically located cell nuclei, a unique feature of DCT cells ( SI Appendix , Fig. S3 A ).…”

Section: Resultssupporting

confidence: 91%

TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival

Mittermeier

Demirkhanyan

Sliwa

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Zn2+, Mg2+, and Ca2+are essential minerals required for a plethora of metabolic processes and signaling pathways. Different categories of cation-selective channels and transporters are therefore required to tightly control the cellular levels of individual metals in a cell-specific manner. However, the mechanisms responsible for the organismal balance of these essential minerals are poorly understood. Herein, we identify a central and indispensable role of the channel-kinase TRPM7 for organismal mineral homeostasis. The function of TRPM7 was assessed by single-channel analysis of TRPM7, phenotyping of TRPM7-deficient cells in conjunction with metabolic profiling of mice carrying kidney- and intestine-restricted null mutations inTrpm7and animals with a global “kinase-dead” point mutation in the gene. The TRPM7 channel reconstituted in lipid bilayers displayed a similar permeability to Zn2+and Mg2+. Consistently, we found that endogenous TRPM7 regulates the total content of Zn2+and Mg2+in cultured cells. Unexpectedly, genetic inactivation of intestinal rather than kidney TRPM7 caused profound deficiencies specifically of Zn2+, Mg2+, and Ca2+at the organismal level, a scenario incompatible with early postnatal growth and survival. In contrast, global ablation of TRPM7 kinase activity did not affect mineral homeostasis, reinforcing the importance of the channel activity of TRPM7. Finally, dietary Zn2+and Mg2+fortifications significantly extended the survival of offspring lacking intestinal TRPM7. Hence, the organismal balance of divalent cations critically relies on one common gatekeeper, the intestinal TRPM7 channel.

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Section: Resultssupporting

confidence: 91%

TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival

Mittermeier

Demirkhanyan

Sliwa

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Although TRPM7 is essential for early embryonic development [10,163,164,165], the contribution of Mg 2+ influx through TRPM7 on the embryonic development remains controversial because TRPM7 acts as both channel and enzyme [10,164]. Several studies support the roles of kinase, which is responsible for the requirement of TRPM7 during embryogenesis [163,164,166]. The depletion of TRPM7 leads to disruption of the embryonic developments without affecting the uptake of Mg 2+ in thymocytes [164].…”

Section: Effects Of Mg2+ On the Cellular Fate And Phenotypementioning

confidence: 99%

Magnesium Is a Key Player in Neuronal Maturation and Neuropathology

Yamanaka

Shindo

Oka

2019

IJMS

106

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Magnesium (Mg) is the second most abundant cation in mammalian cells, and it is essential for numerous cellular processes including enzymatic reactions, ion channel functions, metabolic cycles, cellular signaling, and DNA/RNA stabilities. Because of the versatile and universal nature of Mg2+, the homeostasis of intracellular Mg2+ is physiologically linked to growth, proliferation, differentiation, energy metabolism, and death of cells. On the cellular and tissue levels, maintaining Mg2+ within optimal levels according to the biological context, such as cell types, developmental stages, extracellular environments, and pathophysiological conditions, is crucial for development, normal functions, and diseases. Hence, Mg2+ is pathologically involved in cancers, diabetes, and neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, and demyelination. In the research field regarding the roles and mechanisms of Mg2+ regulation, numerous controversies caused by its versatility and complexity still exist. As Mg2+, at least, plays critical roles in neuronal development, healthy normal functions, and diseases, appropriate Mg2+ supplementation exhibits neurotrophic effects in a majority of cases. Hence, the control of Mg2+ homeostasis can be a candidate for therapeutic targets in neuronal diseases. In this review, recent results regarding the roles of intracellular Mg2+ and its regulatory system in determining the cell phenotype, fate, and diseases in the nervous system are summarized, and an overview of the comprehensive roles of Mg2+ is provided.

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“…These phenotypes were attributed to Mg 2+ deficiency, which was required for alkaline phosphatase activity and mineralization [21]. In addition to reduced enamel volume, another study suggested that TRPM7 was involved in the early stages of amelogenesis via cAMP response element binding protein (CREB) [23]. Therefore, both TRPM7 and CRAC components are expressed in enamel cells, and it would be of interest to understand the potential functional links between these two distinct channels.…”

Section: Introductionmentioning

confidence: 99%

TRPM7 activation potentiates SOCE in enamel cells but requires ORAI

Bomfim

Costiniti

et al. 2020

Cell Calcium

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Calcium (Ca 2+) release-activated Ca 2+ (CRAC) channels mediated by STIM1/2 and ORAI (ORAI1-3) proteins form the dominant store-operated Ca 2+ entry (SOCE) pathway in a variety of cells. Among these, the enamel-forming cells known as ameloblasts rely on CRAC channel function to enable Ca 2+ influx, which is important for enamel mineralization. This key role of the CRAC channel is supported by human mutations and animal models lacking STIM1 and ORAI1, which results in enamel defects and hypomineralization. A number of recent reports have highlighted the role of the chanzyme TRPM7 (transient receptor potential melastanin 7), a transmembrane protein containing an ion channel permeable to divalent cations (Mg 2+ , Ca 2+), as a modulator of SOCE. This raises the question as to whether TRPM7 should be considered an alternative route for Ca 2+ influx, or if TRPM7 modifies CRAC channel activity in enamel cells. To address these questions, we monitored Ca 2+ influx mediated by SOCE using the pharmacological TRPM7 activator naltriben and the inhibitor NS8593 in rat primary enamel cells and in the murine ameloblast cell line LS8 cells stimulated with thapsigargin. We also measured Ca 2+ dynamics in ORAI1/2-deficient (shOrai1/2) LS8 cells and in cells with siRNA knock-down of Trpm7. We found that primary enamel cells stimulated with theTRPM7 activator potentiated Ca 2+ influx via SOCE compared to control cells. However, blockade of TRPM7 with NS8593 did not decrease the SOCE peak. Furthermore, activation of TRPM7 in shOrai1/2 LS8 cells lacking SOCE failed to elicit Ca 2+ influx, and Trpm7 knock-down had no effect on SOCE. Taken together, our data suggest that TRPM7 is a positive modulator of SOCE potentiating Ca 2+ influx in enamel cells, but its function is fully dependent on the prior activation of the ORAI channels.

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The crucial role of the TRPM7 kinase domain in the early stage of amelogenesis

Cited by 16 publications

References 39 publications

TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival

TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival

Magnesium Is a Key Player in Neuronal Maturation and Neuropathology

TRPM7 activation potentiates SOCE in enamel cells but requires ORAI

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