| Flavonoids increase melanin production and reduce proliferation, migration and invasion of melanoma cells by blocking endolysosomal/melanosomal TPC2. | Flavonoids increase melanin production and reduce proliferation, migration and invasion of melanoma cells by blocking endolysosomal/melanosomal TPC2.
Netcharoensirisuk P, Abrahamian C, Tang R, Chen CC, Rosato AS, Beyers W, Chao YK, Filippini A, Di Pietro S, Bartel K, Biel M, Vollmar AM, Umehara K, De-Eknamkul W, Grimm C., Free PMC Article | 11/13/2021 |
| Human genome diversity data reveal that L564P is the predominant TPC2 variant and a prerequisite for the blond hair associated M484L gain-of-function effect. | Human genome diversity data reveal that L564P is the predominant TPC2 variant and a prerequisite for the blond hair associated M484L gain-of-function effect.
Böck J, Krogsaeter E, Passon M, Chao YK, Sharma S, Grallert H, Peters A, Grimm C., Free PMC Article | 04/24/2021 |
| cryo-EM structure of human TPC2 provides insights into the mechanism of PI(3,5)P2-regulated gating of TPC2, which is distinct from that of TPC1 | Structural mechanisms of phospholipid activation of the human TPC2 channel.
She J, Zeng W, Guo J, Chen Q, Bai XC, Jiang Y., Free PMC Article | 04/25/2020 |
| support a role of TPC2 in autophagy progression and extracellular vesicle trafficking in cancer cells | TPC2 mediates autophagy progression and extracellular vesicle secretion in cancer cells.
Sun W, Yue J. | 10/5/2019 |
| PI(3,5)P2-binding site in hTPC2 identified at positively charged amino acids (K203, K204, and K207) in the linker between transmembrane helices S4 and S5 and by S322 in the cytosolic extension of S6 and protein-lipid interface upon mutations of residues within the lipid-binding pocket had neither an effect on the binding behavior nor on the channel's lipid sensitivity. | Phosphatidylinositol-3,5-bisphosphate lipid-binding-induced activation of the human two-pore channel 2.
Kirsch SA, Kugemann A, Carpaneto A, Böckmann RA, Dietrich P., Free PMC Article | 09/29/2018 |
| TPC2 polymorphisms are associated with a hair pigmentation. | TPC2 polymorphisms associated with a hair pigmentation phenotype in humans result in gain of channel function by independent mechanisms.
Chao YK, Schludi V, Chen CC, Butz E, Nguyen ONP, Müller M, Krüger J, Kammerbauer C, Ben-Johny M, Vollmar AM, Berking C, Biel M, Wahl-Schott CA, Grimm C., Free PMC Article | 06/30/2018 |
| Data (including data from studies using tissue from knockout mice) suggest that beta-adrenergic stimulation of pancreas leads to glucagon secretion by hierarchy of calcium signaling in glucagon-secreting cell; such signaling is initiated by cAMP-induced TPC2-dependent calcium release from acidic stores and is further amplified by calcium release from endoplasmic reticulum. | Adrenaline Stimulates Glucagon Secretion by Tpc2-Dependent Ca(2+) Mobilization From Acidic Stores in Pancreatic α-Cells.
Hamilton A, Zhang Q, Salehi A, Willems M, Knudsen JG, Ringgaard AK, Chapman CE, Gonzalez-Alvarez A, Surdo NC, Zaccolo M, Basco D, Johnson PRV, Ramracheya R, Rutter GA, Galione A, Rorsman P, Tarasov AI., Free PMC Article | 06/30/2018 |
| the divergent pore regions from human TPC2, a two-domain channel that holds a key intermediate position in the evolution of voltage-gated ion channels, were characterized. | Isolated pores dissected from human two-pore channel 2 are functional.
Penny CJ, Rahman T, Sula A, Miles AJ, Wallace BA, Patel S., Free PMC Article | 06/9/2018 |
| The ion selectivity of Arabidopsis thaliana TPC1 was compared with the selectivity of human TPC2. HsTPC2 was confirmed as a Na(+)-selective channel activated by phosphatidylinositol 3,5-bisphosphate. The ion permeability ratios of HsTPC2 and its mutants were calculated. | Tuning the ion selectivity of two-pore channels.
Guo J, Zeng W, Jiang Y., Free PMC Article | 05/12/2018 |
| These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells. | Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells.
Jahidin AH, Stewart TA, Thompson EW, Roberts-Thomson SJ, Monteith GR. | 05/20/2017 |
| Results demonstrated the unique bell-shaped regulation of hTPC2 channel activity by [NAADP] and that channel activity is modulated by PKA phosphorylation at position S666. | Characterization of Two-Pore Channel 2 by Nuclear Membrane Electrophysiology.
Lee CS, Tong BC, Cheng CW, Hung HC, Cheung KH., Free PMC Article | 01/28/2017 |
| TPC2 regulates pigmentation through two fundamental determinants of melanosome function: pH and size. | TPC2 controls pigmentation by regulating melanosome pH and size.
Ambrosio AL, Boyle JA, Aradi AE, Christian KA, Di Pietro SM., Free PMC Article | 12/17/2016 |
| rs1551305 single nucleotide polymorphism is associated with type 2 diabetes risk. | Genetic Variants of TPCN2 Associated with Type 2 Diabetes Risk in the Chinese Population.
Fan Y, Li X, Zhang Y, Fan X, Zhang N, Zheng H, Song Y, Shen C, Shen J, Ren F, Yang J., Free PMC Article | 07/30/2016 |
| Results show that PDGs use previously unknown mechanisms of membrane dynamics and content exchange that are regulated by TPC2. | TPC2 mediates new mechanisms of platelet dense granule membrane dynamics through regulation of Ca2+ release.
Ambrosio AL, Boyle JA, Di Pietro SM., Free PMC Article | 07/2/2016 |
| Here, using live cell imaging, the authors obtained evidence that in contrast to the new model, ebolavirus enters cells through endolysosomes that contain both NPC1 and TPC2. | Ebolavirus Glycoprotein Directs Fusion through NPC1+ Endolysosomes.
Simmons JA, D'Souza RS, Ruas M, Galione A, Casanova JE, White JM., Free PMC Article | 04/30/2016 |
| Studies suggest that both two-pore channels TPC1 and TPC2 as nicotinic acid adenine dinucleotide phosphate (NAADP) targets. | Function and dysfunction of two-pore channels.
Patel S. | 04/23/2016 |
| TPC2 is thus a potential drug target within a pathogenic LRRK2 cascade that disrupts Ca(2+)-dependent trafficking in Parkinson disease | Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition.
Hockey LN, Kilpatrick BS, Eden ER, Lin-Moshier Y, Brailoiu GC, Brailoiu E, Futter CE, Schapira AH, Marchant JS, Patel S., Free PMC Article | 03/5/2016 |
| SNPs within Tpcn2 are associated with fasting insulin in humans. | Identification of a novel gene for diabetic traits in rats, mice, and humans.
Tsaih SW, Holl K, Jia S, Kaldunski M, Tschannen M, He H, Andrae JW, Li SH, Stoddard A, Wiederhold A, Parrington J, Ruas da Silva M, Galione A, Meigs J, Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) Investigators, Hoffmann RG, Simpson P, Jacob H, Hessner M, Solberg Woods LC., Free PMC Article | 07/25/2015 |
| NAADP induced marked Ca(2+) transients in HEK293 cells that stably coexpressed hTPC2 with hTPC1 or cTPC3, but failed to evoke any such response in cells that coexpressed interacting hTPC2 and rTPC3 subunits | Organelle-specific subunit interactions of the vertebrate two-pore channel family.
Ogunbayo OA, Zhu Y, Shen B, Agbani E, Li J, Ma J, Zhu MX, Evans AM., Free PMC Article | 04/25/2015 |
| TPC2, but not TPC1, caused a proliferation of endolysosomal structures, dysregulating intracellular trafficking, and cellular pigmentation. | The Two-pore channel (TPC) interactome unmasks isoform-specific roles for TPCs in endolysosomal morphology and cell pigmentation.
Lin-Moshier Y, Keebler MV, Hooper R, Boulware MJ, Liu X, Churamani D, Abood ME, Walseth TF, Brailoiu E, Patel S, Marchant JS., Free PMC Article | 04/25/2015 |
| These results demonstrate that a VEGFR2/NAADP/TPC2/Ca(2+) signaling pathway is critical for VEGF-induced angiogenesis | VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2-dependent Ca2+ signaling.
Favia A, Desideri M, Gambara G, D'Alessio A, Ruas M, Esposito B, Del Bufalo D, Parrington J, Ziparo E, Palombi F, Galione A, Filippini A., Free PMC Article | 04/18/2015 |
| TPC1 and TPC2 proteins play a key role in Ebola virus infection and may be effective targets for antiviral therapy. | Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment.
Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE, Klugbauer N, Grimm C, Wahl-Schott C, Biel M, Davey RA., Free PMC Article | 04/4/2015 |
| Notably, NAADP-mediated Ca(2+) release in intact cells is regulated by Mg(2+), PI(3,5)P2, and P38/JNK kinases, thus paralleling regulation of TPC2 currents. | Convergent regulation of the lysosomal two-pore channel-2 by Mg²⁺, NAADP, PI(3,5)P₂ and multiple protein kinases.
Jha A, Ahuja M, Patel S, Brailoiu E, Muallem S., Free PMC Article | 04/26/2014 |
| These results provide strong evidence for modulation of store-operated Ca(2+) entry by TPC2 involving de novo association between TPC2 and STIM1, as well as Orai1, in human cells. | Two-pore channel 2 (TPC2) modulates store-operated Ca(2+) entry.
López J, Dionisio N, Berna-Erro A, Galán C, Salido GM, Rosado JA. | 11/24/2012 |
| TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+. | TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+.
Pitt SJ, Funnell TM, Sitsapesan M, Venturi E, Rietdorf K, Ruas M, Ganesan A, Gosain R, Churchill GC, Zhu MX, Parrington J, Galione A, Sitsapesan R., Free PMC Article | 12/4/2010 |