更新于：2024-11-01

TRPML3 x TRPML2

更新于：2024-11-01

基本信息

关联

项与 TRPML3 x TRPML2 相关的药物

ML-SI3

靶点

TRPML1 x TRPML2 x TRPML3

作用机制

TRPML1 inhibitors [+2]

在研机构

Ludwig-Maximilians-Universität München

原研机构

Ludwig-Maximilians-Universität München

在研适应症-

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

ML122

靶点

TRPML2 x TRPML3

作用机制

TRPML2 agonists [+1]

在研机构

The UAMS Translational Research Institute

原研机构

The UAMS Translational Research Institute

在研适应症-

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TRPML3 x TRPML2 相关的临床结果

登录后查看更多信息

100 项与 TRPML3 x TRPML2 相关的转化医学

登录后查看更多信息

0 项与 TRPML3 x TRPML2 相关的专利（医药）

登录后查看更多信息

项与 TRPML3 x TRPML2 相关的文献（医药）

2024-03-01·Journal of Veterinary Research

Tissue expression of porcine transient receptor potential mucolipin protein channels and their differential responses to porcine reproductive and respiratory syndrome virus infection in vitro

Article

作者: Xie, Lixia ; Lan, Ying ; Hong, Xinyi ; Xia, Zhiqiang ; Long, Denggao

AbstractIntroductionPorcine reproductive and respiratory syndrome virus (PRRSV) infection results in a serious disease, posing a huge economic threat to the global swine industry. The transient receptor potential mucolipin proteins (TRPMLs) have been shown to be strongly associated with virus infection and other physiological processes in humans, but their tissue distribution and responses to PRRSV in pigs remain unknown.Material and MethodsQuantitative reverse-transcription PCR analysis was undertaken to determine the optimal primer for TRPML expression detection and for quantifying that expression individually in different pig tissue samples. Meat Animal Research Center 145 (MARC-145) monkey kidney cells and the TRPML-specific activator mucolipin synthetic agonist 1 (ML-SA1) were used to reveal the relationship between TRPML and PRRSV-2 infection.ResultsThe best primers for each TRPML gene used in a fluorescence-based quantitative method were identified and TRPML1 was found to be highly expressed in the kidneys and liver of pigs, while TRPML2 and TRPML3 were observed to be primarily expressed in the kidney and spleen tissues. The expression of TRPML2 was upregulated with the rise in PRRSV-2 infection titre but not the expression of TRPML1 or TRPML3, and ML-SA1 inhibited PRRSV-2 in a dose-dependent manner.ConclusionOur research revealed the gene expression of TRPMLs in pigs and identified that TRPML channels may act as key host factors against PRRSV infection, which could lead to new targets for the prevention and treatment of pig infectious diseases.

2023-05-01·Gene

Gene expression of TRPMLs and its regulation by pathogen stimulation

Article

作者: Hong, Xinyi ; Xie, Lixia ; Qin, Chenhu ; Xia, Zhiqiang ; Li, Dongyuan

The transient receptor potential mucolipin (TRPML) subfamily in mammalian has three members, namely TRPML1, TRPML2, and TRPML3, who play key roles in regulating intracellular Ca²⁺ homeostasis, endosomal pH, membrane trafficking and autophagy. Previous studies had shown that three TRPMLs are closely related to the occurrence of pathogen invasion and immune regulation in some immune tissues or cells, but the relationship between TRPMLs expression and pathogen invasion in lung tissue or cell remains elusive. Here, we investigated the expression distribution of three TRPML channels in mouse different tissues by qRT-PCR, and then found that all three TRPMLs were highly expressed in the mouse lung tissue, as well as mouse spleen and kidney tissues. The expression of TRPML1 or TRPML3 in all three mouse tissues had a significant down-regulation after the treatment of Salmonella or LPS, but TRPML2 expression showed a remarkable increase. Consistently, TRPML1 or TRPML3 but not TRPML2 in A549 cells also displayed a decreased expression induced by LPS stimulation, which shared a similar regulation pattern in the mouse lung tissue. Furthermore, the treatment of the TRPML1 or TRPML3 specific activator induced a dose-dependent up-regulation of inflammatory factors IL-1β, IL-6 and TNFα, suggesting that TRPML1 and TRPML3 are likely to play an important role in immune and inflammatory regulation. Together, our study identified the gene expression of TRPMLs induced by pathogen stimulation in vivo and in vitro, which may provide novel targets for innate immunity or pathogen regulation.

2022-02-01·Journal of Biological Chemistry2区 · 生物学

Cryo-EM structure of mouse TRPML2 in lipid nanodiscs

2区 · 生物学

Article

作者: McCormick, Peter J ; Ye, Heyang ; Duan, Jingjing ; Zhang, Yuting ; Tian, Miao ; Zhang, Jin ; Li, Jian ; Zhu, Huaiyi ; Zeng, Bo ; Fu, Yang ; Hu, Xiaohui ; Song, Xiaojing ; Cao, Yanru

In mammalians, transient receptor potential mucolipin ion channels (TRPMLs) exhibit variable permeability to cations such as Ca²⁺, Fe²⁺, Zn²⁺, and Na⁺ and can be activated by the phosphoinositide PI(3,5)P2 in the endolysosomal system. Loss or dysfunction of TRPMLs has been implicated in lysosomal storage disorders, infectious diseases, and metabolic diseases. TRPML2 has recently been identified as a mechanosensitive and hypotonicity-sensitive channel in endolysosomal organelles, which distinguishes it from TRPML1 and TRPML3. However, the molecular and gating mechanism of TRPML2 remains elusive. Here, we present the cryo-EM structure of the full-length mouse TRPML2 in lipid nanodiscs at 3.14 Å resolution. The TRPML2 homotetramer structure at pH 7.4 in the apo state reveals an inactive conformation and some unique features of the extracytosolic/luminal domain and voltage sensor-like domain that have implications for the ion-conducting pathway. This structure enables new comparisons between the different subgroups of TRPML channels with available structures and provides structural insights into the conservation and diversity of TRPML channels. These comparisons have broad implications for understanding a variety of molecular mechanisms of TRPMLs in different pH conditions, including with and without bound agonists and antagonists.