Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Islam, Shahidul

doi:10.3390/cells9030685

Cited by 26 publications

(36 citation statements)

References 150 publications

(269 reference statements)

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“…Notably, by analyzing the RNA sequencing data, Marabita and Islam reported that TRPC1 is the only TRPC channel which is expressed in human pancreatic β-cells [ 208 , 209 ]. Therefore, the information related to the roles of TRPC3, TRPC4, TRPC5, and TRPC6 channels in animal pancreatic β-cell models may not be applicable to human β-cells.…”

Section: Physiological and Pathological Functions Of Trpcs Revealementioning

confidence: 99%

Transient Receptor Potential Canonical (TRPC) Channels: Then and Now

Chen

Sooch

Demaree

et al. 2020

Cells

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Twenty-five years ago, the first mammalian Transient Receptor Potential Canonical (TRPC) channel was cloned, opening the vast horizon of the TRPC field. Today, we know that there are seven TRPC channels (TRPC1–7). TRPCs exhibit the highest protein sequence similarity to the Drosophila melanogaster TRP channels. Similar to Drosophila TRPs, TRPCs are localized to the plasma membrane and are activated in a G-protein-coupled receptor-phospholipase C-dependent manner. TRPCs may also be stimulated in a store-operated manner, via receptor tyrosine kinases, or by lysophospholipids, hypoosmotic solutions, and mechanical stimuli. Activated TRPCs allow the influx of Ca2+ and monovalent alkali cations into the cytosol of cells, leading to cell depolarization and rising intracellular Ca2+ concentration. TRPCs are involved in the continually growing number of cell functions. Furthermore, mutations in the TRPC6 gene are associated with hereditary diseases, such as focal segmental glomerulosclerosis. The most important recent breakthrough in TRPC research was the solving of cryo-EM structures of TRPC3, TRPC4, TRPC5, and TRPC6. These structural data shed light on the molecular mechanisms underlying TRPCs’ functional properties and propelled the development of new modulators of the channels. This review provides a historical overview of the major advances in the TRPC field focusing on the role of gene knockouts and pharmacological tools.

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Section: Physiological and Pathological Functions Of Trpcs Revealementioning

confidence: 99%

Transient Receptor Potential Canonical (TRPC) Channels: Then and Now

Chen

Sooch

Demaree

et al. 2020

Cells

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“…The TRPM2 channel is also present in the lysosomes of pancreatic β-cells and possibly endothelial cells [ 36 , 80 , 81 ] and in the mitochondria of hippocampal neurons [ 82 ]. There is increasing evidence to support an important role for the TRPM2 channel in mediating or regulating many physiological processes, such as insulin secretion, inflammatory cytokine production, phagosome maturation and temperature sensing, and interested readers can consult reviews on these topics [ 13 , [83] , [84] , [85] , [86] , [87] , [88] ].…”

Section: Trpm2 Channel Properties Activation Mechanisms and Pharmacmentioning

confidence: 99%

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

Malko

Jiang

2020

Redox Biology

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Oxidative stress resulting from the accumulation of high levels of reactive oxygen species is a salient feature of, and a well-recognised pathological factor for, diverse pathologies. One common mechanism for oxidative stress damage is via the disruption of intracellular ion homeostasis to induce cell death. TRPM2 is a non-selective Ca 2+ -permeable cation channel with a wide distribution throughout the body and is highly sensitive to activation by oxidative stress. Recent studies have collected abundant evidence to show its important role in mediating cell death induced by miscellaneous oxidative stress-inducing pathological factors, both endogenous and exogenous, including ischemia/reperfusion and the neurotoxicants amyloid-β peptides and MPTP/MPP + that cause neuronal demise in the brain, myocardial ischemia/reperfusion, proinflammatory mediators that disrupt endothelial function, diabetogenic agent streptozotocin and diabetes risk factor free fatty acids that induce loss of pancreatic β-cells, bile acids that damage pancreatic acinar cells, renal ischemia/reperfusion and albuminuria that are detrimental to kidney cells, acetaminophen that triggers hepatocyte death, and nanoparticles that injure pericytes. Studies have also shed light on the signalling mechanisms by which these pathological factors activate the TRPM2 channel to alter intracellular ion homeostasis leading to aberrant initiation of various cell death pathways. TRPM2-mediated cell death thus emerges as an important mechanism in the pathogenesis of conditions including ischemic stroke, neurodegenerative diseases, cardiovascular diseases, diabetes, pancreatitis, chronic kidney disease, liver damage and neurovascular injury. These findings raise the exciting perspective of targeting the TRPM2 channel as a novel therapeutic strategy to treat such oxidative stress-associated diseases.

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“…By using TPC1 and TPC2 knock-out in vivo models, we reported that VEGF-induced neo-angiogenesis occurred through the regulation of the VEGFR2/NAADP/TPC2/Ca 2+ signalling pathway [ 14 ]. More generally, Ca 2+ signals have been shown to play a role in cancer, including melanoma, in various ways [ 15 ]. Store-operated calcium entry (SOCE) is an important Ca 2+ signalling mechanism.…”

Section: Introductionmentioning

confidence: 99%

Loss of Two-Pore Channel 2 (TPC2) Expression Increases the Metastatic Traits of Melanoma Cells by a Mechanism Involving the Hippo Signalling Pathway and Store-Operated Calcium Entry

D’Amore

Hanbashi

Agostino

et al. 2020

Cancers

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Melanoma is one of the most aggressive and treatment-resistant human cancers. The two-pore channel 2 (TPC2) is located on late endosomes, lysosomes and melanosomes. Here, we characterized how TPC2 knockout (KO) affected human melanoma cells derived from a metastatic site. TPC2 KO increased these cells’ ability to invade the extracelullar matrix and was associated with the increased expression of mesenchymal markers ZEB-1, Vimentin and N-Cadherin, and the enhanced secretion of MMP9. TPC2 KO also activated genes regulated by YAP/TAZ, which are key regulators of tumourigenesis and metastasis. Expression levels of ORAI1, a component of store-operated Ca2+ entry (SOCE), and PKC-βII, part of the HIPPO pathway that negatively regulates YAP/TAZ activity, were reduced by TPC2 KO and RNA interference knockdown. We propose a cellular mechanism mediated by ORAI1/Ca2+/PKC-βII to explain these findings. Highlighting their potential clinical significance, patients with metastatic tumours showed a reduction in TPC2 expression. Our research indicates a novel role of TPC2 in melanoma. While TPC2 loss may not activate YAP/TAZ target genes in primary melanoma, in metastatic melanoma it could activate such genes and increase cancer aggressiveness. These findings aid the understanding of tumourigenesis mechanisms and could provide new diagnostic and treatment strategies for skin cancer and other metastatic cancers.

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Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Cited by 26 publications

References 150 publications

Transient Receptor Potential Canonical (TRPC) Channels: Then and Now

Transient Receptor Potential Canonical (TRPC) Channels: Then and Now

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

Loss of Two-Pore Channel 2 (TPC2) Expression Increases the Metastatic Traits of Melanoma Cells by a Mechanism Involving the Hippo Signalling Pathway and Store-Operated Calcium Entry

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