The TRPM7 kinase limits receptor-induced calcium release by regulating heterotrimeric G-proteins

Suzuki, Shingo; Lis, Annette; Schmitz, C.; Penner, Reinhold; Fleig, Andrea

doi:10.1007/s00018-018-2786-z

Cited by 7 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Store operated Ca 2+ entry is essential for mast cell activation in vitro and in vivo [ 48 , 49 ]. Recently, TRPM7 has been implicated in receptor-induced Ca 2+ release as well as store-operated Ca 2+ entry [ 9 , 12 ]. In primary human lung mast cells (HLMCs) and in the human mast cell lines, LAD2 and HMC-1, TRPM7 expression and function was shown to be essential for cell survival.…”

Section: The Channel-kinase Trpm7 In Immune Cell Signallingmentioning

confidence: 99%

“…The melastatin-like TRPM7 channel conducts divalent cations, specifically calcium (Ca 2+ ), magnesium (Mg 2+ ) and zinc (Zn 2+ ) [ 1 , 2 , 3 ]. It has been implicated in cellular and systemic Mg 2+ homeostasis [ 4 , 5 , 6 ], Zn 2+ -mediated toxicity [ 7 , 8 ] and intracellular Ca 2+ signalling [ 9 , 10 , 11 , 12 ]. The TRPM7 channel is considered to be constitutively active and its activity to be negatively regulated by intracellular cations (Mg 2+ , Ba 2+ , Sr 2+ , Zn 2+ , Mn 2+ ), Mg-ATP, polyamines, chloride (Cl − ) and bromide (Br − ) concentrations, low intracellular pH and hydrolysis of the acidic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP 2 ) [ 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis

Nadolni¹,

Zierler²

2018

Cells

View full text Add to dashboard Cite

The enzyme-coupled transient receptor potential channel subfamily M member 7, TRPM7, has been associated with immunity and immune cell signalling. Here, we review the role of this remarkable signalling protein in lymphocyte proliferation, differentiation, activation and survival. We also discuss its role in mast cell, neutrophil and macrophage function and highlight the potential of TRPM7 to regulate immune system homeostasis. Further, we shed light on how the cellular signalling cascades involving TRPM7 channel and/or kinase activity culminate in pathologies as diverse as allergic hypersensitivity, arterial thrombosis and graft versus host disease (GVHD), stressing the need for TRPM7 specific pharmacological modulators.

show abstract

Section: The Channel-kinase Trpm7 In Immune Cell Signallingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis

Nadolni¹,

Zierler²

2018

Cells

View full text Add to dashboard Cite

show abstract

“…Patch clamp experiments were performed in the whole-cell configuration 40 . Currents were elicited by a ramp protocol from −100 mV to +100 mV over 50 ms acquired at 0.5 kHz and a holding potential of 0 mV.…”

Section: Electrophysiologymentioning

confidence: 99%

TRPM7 contributes to progressive nephropathy

Suzuki

Penner

Fleig

2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

TRPM7 belongs to the Transient Receptor Potential Melastatin family of ion channels and is a divalent cation-conducting ion channel fused with a functional kinase. TRPM7 plays a key role in a variety of diseases, including neuronal death in ischemia, cancer, cardiac atrial fibrillation, malaria invasion. TRPM7 is aberrantly over-expressed in lung, liver and heart fibrosis. It is also overexpressed after renal ischemia-reperfusion, an event that induces kidney injury and fibrosis. However, the role of TRPM7 in kidney fibrosis is unclear. Using the unilateral ureteral obstruction (UUO) mouse model, we examined whether TRPM7 contributes to progressive renal damage and fibrosis. We find that TRPM7 expression increases in UUO kidneys. Systemic application of NS8593, a known TRPM7 inhibitor, prevents kidney atrophy in UUO kidneys, retains tubular formation, and reduces TRPM7 expression to normal levels. Cell proliferation of both tubular epithelial cells and interstitial cells is reduced by NS8593 treatment in UUO kidneys, as are TGF-β1/Smad signaling events. We conclude that TRPM7 is upregulated during inflammatory renal damage and propose that pharmacological intervention targeting TRPM7 may prove protective in progressive kidney fibrosis.TRPM7 belongs to the Transient Receptor Potential (TRP) Melastatin family of ion channels, but is unique in that its ion channel domain is fused with a functional serine/threonine kinase 1 . TRPM7 was the first ion channel shown to conduct a range of divalent cations 2,3 , including physiologically essential divalent cations such as Ca 2+ , Mg 2+ , Zn 2+ , Ni 2+ , Mn 2+ , and Co 2+ . Ample evidence supports TRPM7 to be critical in regulating Mg 2+ homeostasis 1 and play a key role in a variety of diseases, including neuronal death in ischemia 4 , renal ischemia 5 , and cardiac atrial fibrillation 6 . TRPM7 is expressed ubiquitously in mammals, and is key in driving cell growth and proliferation, linking the protein to hyperproliferative diseases such cancer 1,7,8 and pulmonary, hepatic, and cardiac fibrosis 6,9-12 . Tissue fibrosis refers to a number of conditions that cause interstitial organ damage followed by inflammation and maladaptive wound healing eventually leading to fibrosis and chronic disease in the organ affected. TRPM7 overexpression leads to fibrosis through the TGF-β signaling pathway 9-11 . Recent in vitro data show that TRPM7 plays a pivotal role in progressive inflammatory and fibrotic disease by promoting excessive extracellular matrix (ECM) deposition 9 . It regulates proliferation and differentiation of fibroblasts 11 and proliferation and polarization of macrophages 13 as well as their Ca 2+ -dependent activation 14 . A recent study supports this hypothesis, as genetic suppression of TRPM7 in a kidney transplantation mouse model alleviated progressive inflammatory kidney fibrosis 15 .In the kidney, cell proliferation is a central response to injury that culminates in the development of fibrosis and renal failure. Unilateral ureteral obstruction (UUO) is a wide...

show abstract

“…entry (9,12). In primary human lung mast cells (HLMCs) and in the human mast cell lines, LAD2 and HMC-1, TRPM7 expression and function was shown to be essential for cell survival.…”

Section: The Channel-kinase Trpm7 In Immune Cell Signallingmentioning

confidence: 99%

“…The melastatin-like TRPM7 channel conducts divalent cations, specifically calcium (Ca 2+ ), magnesium (Mg 2+ ) and zinc (Zn 2+ ) (1)(2)(3). It has been implicated in cellular and systemic Mg 2+ homeostasis(4-6), Zn 2+ -mediated toxicity (7,8) and intracellular Ca 2+ signalling (9)(10)(11)(12). The TRPM7 channel is considered to be constitutively active and its activity to be negatively regulated via intracellular cations (Mg 2+ , Ba 2+ , Sr 2+ , Zn 2+ , Mn 2+ ), Mg-ATP, chloride (Cl -) and bromide (Br -) concentrations, low intracellular pH and hydrolysis of the acidic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP 2 ) (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis

Nadolni¹,

Zierler²

2018

Preprint

View full text Add to dashboard Cite

The enzyme-coupled transient receptor potential channel subfamily M member 7, TRPM7, has been associated with immunity and immune cell signalling. Here, we review the role of this remarkable signalling protein in lymphocyte proliferation, differentiation, activation and survival. We also discuss its role in mast cell, neutrophil and macrophage function and highlight the potential of TRPM7 to regulate immune system homeostasis. Further, we shed light on how the cellular signalling cascades involving TRPM7 channel and/or kinase activity culminate in pathologies as diverse as allergic hypersensitivity, arterial thrombosis, and graft versus host disease (GVHD), stressing the need for TRPM7 specific pharmacological modulators.

show abstract

The TRPM7 kinase limits receptor-induced calcium release by regulating heterotrimeric G-proteins

Cited by 7 publications

References 32 publications

The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis

The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis

TRPM7 contributes to progressive nephropathy

The Channel-Kinase TRPM7 as Novel Regulator of Immune System Homeostasis

Contact Info

Product

Resources

About