Reciprocal regulation of actin cytoskeleton remodelling and cell migration by calcium and zinc: role of TRPM2 channels

Li, Fangfang; Abuarab, Nada; Sivaprasadarao, Asipu

doi:10.1242/jcs.179796

Cited by 46 publications

(64 citation statements)

References 57 publications

(41 reference statements)

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“…9 Whether TRPM2-mediated Zn 2C signalling plays a role in this process is not known, but we have demonstrated that TRPM2 inhibition as well as Zn 2C chelation inhibits PC-3 and HeLa cell migration. 10 In conclusion, the stress signalling pathway identified in our study has provided new fundamental knowledge on how ionic signalling facilitates inter-organelle communication to drive mitochondrial fragmentation. The results have implications for a number of human diseases including cancer, and may have therapeutic potential.…”

mentioning

confidence: 64%

Ionic signalling and mitochondrial dynamics

Abuarab

Sivaprasadarao

2017

Molecular & Cellular Oncology

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In age-related diseases, rise in intracellular reactive oxygen species (ROS) causes fragmentation of mitochondrial network. Our recent study demonstrated that ROS activation of TRPM2 (transient receptor potential melastatin-2) channels triggers lysosomal Zn release that, in turn, triggers mitochondrial fragmentation. The findings provide new mechanistic insights that may have therapeutic implications.

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confidence: 64%

Ionic signalling and mitochondrial dynamics

Abuarab

Sivaprasadarao

2017

Molecular & Cellular Oncology

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“…It is also interesting to note that the distribution of Orai1 amongst the liver subcellular fractions is quite different from that of TRPM2. It is thought that TRPM2 principally functions at the PM, but may also be present in lysosomes, and is also likely to be trafficked to and from the PM [67,68].…”

Section: Discussionmentioning

confidence: 99%

Evidence for the interaction of peroxiredoxin-4 with the store-operated calcium channel activator STIM1 in liver cells

et al. 2018

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Ca entry through store-operated Ca channels (SOCs) in the plasma membrane (PM) of hepatocytes plays a central role in the hormonal regulation of liver metabolism. SOCs are composed of Orai1, the channel pore protein, and STIM1, the activator protein, and are regulated by hormones and reactive oxygen species (ROS). In addition to Orai1, STIM1 also interacts with several other intracellular proteins. Most previous studies of the cellular functions of Orai1 and STIM1 have employed immortalised cells in culture expressing ectopic proteins tagged with a fluorescent polypeptide such as GFP. Little is known about the intracellular distributions of endogenous Orai1 and STIM1. The aims are to determine the intracellular distribution of endogenous Orai1 and STIM1 in hepatocytes and to identify novel STIM1 binding proteins. Subcellular fractions of rat liver were prepared by homogenisation and differential centrifugation. Orai1 and STIM1 were identified and quantified by western blot. Orai1 was found in the PM (0.03%), heavy (44%) and light (27%) microsomal fractions, and STIM1 in the PM (0.09%), and heavy (85%) and light (13%) microsomal fractions. Immunoprecipitation of STIM1 followed by LC/MS or western blot identified peroxiredoxin-4 (Prx-4) as a potential STIM1 binding protein. Prx-4 was found principally in the heavy microsomal fraction. Knockdown of Prx-4 using siRNA, or inhibition of Prx-4 using conoidin A, did not affect Ca entry through SOCs but rendered SOCs susceptible to inhibition by HO. It is concluded that, in hepatocytes, a considerable proportion of endogenous Orai1 and STIM1 is located in the rough ER. In the rough ER, STIM1 interacts with Prx-4, and this interaction may contribute to the regulation by ROS of STIM1 and SOCs.

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“…Maintenance of acidic pH of lysosomes [75,76] Decrease of dentinogenesis and dental bone formation in CLC-7 deficient mice [77,78] Degradation of fAβ which drives AD [79,80] Osteopetrosis in CLC-7 mutation [81][82][83][84] LSD and neurodegeneration in CLC-7-deficient mice [64,82] CFTR Support lysosomal acidification [85] Decrease of bacteria killing function and phago-lysosomal fusion in macrophage [86] TRPM2 Induce DC maturation and migration [87] Increase of actin remodeling [88] Increase of pancreatic β cell apoptosis [89] Increase LMP, NLRP3 inflammasome, and mitochondrial fission on the plasma membrane [90,91]…”

Section: Clc-3mentioning

confidence: 99%

“…Thus, the Ca 2+ ion influx through TRPM2 plays multifunctional roles [141][142][143]. TRPM2 is also localized on the lysosomal membrane and modulates cellular functions such as cell migration, cytoskeleton remodeling, and apoptosis [87][88][89]. On the lysosomal membrane of dendritic cells (DC), TRPM2 releases Ca 2+ ions to the cytoplasm to mediate optimal DC maturation and DC migration and homing to lymph nodes [87].…”

Section: Trpm2mentioning

confidence: 99%

“…On the lysosomal membrane of dendritic cells (DC), TRPM2 releases Ca 2+ ions to the cytoplasm to mediate optimal DC maturation and DC migration and homing to lymph nodes [87]. H 2 O 2 -induced Ca 2+ influx increases through lysosomal TRPM2 and triggers actin remodeling, which, subsequently, activates cell migration, even though the extracellular Ca 2+ entry does not affect the cytoskeletal remodeling [88]. Additionally, lysosomal TRPM2 Ca 2+ ion release in pancreatic β cells induces apoptosis [89].…”

Section: Trpm2mentioning

confidence: 99%

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Nanoparticle-Mediated Therapeutic Application for Modulation of Lysosomal Ion Channels and Functions

Lee¹,

Hong²

2020

Pharmaceutics

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Applications of nanoparticles in various fields have been addressed. Nanomaterials serve as carriers for transporting conventional drugs or proteins through lysosomes to various cellular targets. The basic function of lysosomes is to trigger degradation of proteins and lipids. Understanding of lysosomal functions is essential for enhancing the efficacy of nanoparticles-mediated therapy and reducing the malfunctions of cellular metabolism. The lysosomal function is modulated by the movement of ions through various ion channels. Thus, in this review, we have focused on the recruited ion channels for lysosomal function, to understand the lysosomal modulation through the nanoparticles and its applications. In the future, lysosomal channels-based targets will expand the therapeutic application of nanoparticles-associated drugs.

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Reciprocal regulation of actin cytoskeleton remodelling and cell migration by calcium and zinc: role of TRPM2 channels

Abstract: ABSTRACT

Cited by 46 publications

References 57 publications

Ionic signalling and mitochondrial dynamics

Ionic signalling and mitochondrial dynamics

Evidence for the interaction of peroxiredoxin-4 with the store-operated calcium channel activator STIM1 in liver cells

Nanoparticle-Mediated Therapeutic Application for Modulation of Lysosomal Ion Channels and Functions

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