Ask about this productRelated genes to: TMEM168 Blocking Peptide
- Gene:
- TMEM168 NIH gene
- Name:
- transmembrane protein 168
- Previous symbol:
- -
- Synonyms:
- DKFZp564C012,FLJ13576
- Chromosome:
- 7q31.1
- Locus Type:
- gene with protein product
- Date approved:
- 2006-08-08
- Date modifiied:
- 2016-10-05
Related products to: TMEM168 Blocking Peptide
Related articles to: TMEM168 Blocking Peptide
- Transmembrane protein 168 (TMEM168) was found to be localized on the nuclear membrane. A heterozygous mutation (c.1616G>A, p. R539Q) in TMEM168 was identified in patients with Brugada syndrome. This mutation reduced expression of cardiomyocyte sodium channel Nav1.5 via Nedd4-2 E3 ubiquitin ligase-induced ubiquitination and degradation. However, the detailed molecular mechanism provoked by the TMEM168 mutant remains unclear. Here, we demonstrated that small heat shock protein αB-crystallin, which can bind to Nav1.5 and Nedd4-2 and interfere with the association of both proteins, was strongly recruited from the cell surface to the perinuclear region because of the much higher affinity of αB-crystallin with the TMEM168 mutant than with wild-type TMEM168. Following knockdown of αB-crystallin in HL-1 cardiomyocytes, the interaction of Nav1.5 with Nedd4-2 was increased, despite the reduced expression of Nav1.5. Moreover, reduction of Nav1.5 expression by αB-crystallin knockdown was rescued in the presence of a proteasome inhibitor MG-132, suggesting the importance of the αB-crystallin-modulated ubiquitin-proteasome system for the stability of Nav1.5 expression. Collectively, the balance of molecular interactions among Nav1.5, Nedd4-2 and αB-crystallin plays a role in the regulation of cardiomyocyte cell surface expression of Nav1.5, and the TMEM168 mutant disturbs this balance, resulting in a decrease in Nav1.5 expression. - Source: PubMed
Nguyen Le Kim ChiShimizu AkioSoh Joanne Ern ChiKomeno MasahiroSato AkiraOgita Hisakazu - Shati/Nat8l and TMEM168 were identified from nucleus accumbens (NAcc), which received continuous methamphetamine treatments. Shati/Nat8l is a synthetic enzyme that produces N-acetylaspartate (NAA) from L-aspartate and acetyl-coenzyme NAA is converted into N-acetylaspartylglutamate (NAAG) by NAAG synthetase (NAAGS). NAAG works as a highly selective endogenous agonist for the metabotropic glutamate type 3 receptor (mGluR3). We attempted to microinjection of adeno associated virus (AAV) including Shati/Nat8l into mice NAcc. These NAcc-Shati/Nat8l mice showed attenuation of the pharmacological effects of methamphetamine. NAcc-Shati or TMEM168 mice were also produced by AAV strategy and these mice also attenuated the methamphetamine-induced hyper locomotion and place preference test. TMEM168 interacts with osteopontin in NAcc of mice and cultured cells. Further, osteopontin it self has suppressive effects of methamphetamine. TMEM168 enhances anxiety in the elevated-plus maze and light-dark box test. The anxiety is recovered by the treatment of antianxiety drug diazepam. There our serial studies demonstrate that investigation of drug dependence-related molecule could lead to new pathway for new target for psychiatric disease. - Source: PubMed
Nitta Atsumi - Brugada syndrome (BrS) is an inherited channelopathy responsible for almost 20% of sudden cardiac deaths in patients with nonstructural cardiac diseases. Approximately 70% of BrS patients, the causative gene mutation(s) remains unknown. In this study, we used whole exome sequencing to investigate candidate mutations in a family clinically diagnosed with BrS. A heterozygous 1616G>A substitution (R539Q mutation) was identified in the transmembrane protein 168 (TMEM168) gene of symptomatic individuals. Similar to endogenous TMEM168, both TMEM168 wild-type (WT) and mutant proteins that were ectopically induced in HL-1 cells showed nuclear membrane localization. A significant decrease in Na current and Na 1.5 protein expression was observed in HL-1 cardiomyocytes expressing mutant TMEM168. Ventricular tachyarrhythmias and conduction disorders were induced in the heterozygous Tmem168 1616G>A knock-in mice by pharmacological stimulation, but not in WT mice. Na current was reduced in ventricular cardiomyocytes isolated from the Tmem168 knock-in heart, and Na 1.5 expression was also impaired. This impairment was dependent on increased Nedd4-2 binding to Na 1.5 and subsequent ubiquitination. Collectively, our results show an association between the TMEM168 1616G>A mutation and arrhythmogenesis in a family with BrS. - Source: PubMed
Publication date: 2020/03/16
Shimizu AkioZankov Dimitar PSato AkiraKomeno MasahiroToyoda FutoshiYamazaki SatoruMakita ToshinoriNoda TaichiIkawa MasahitoAsano YoshihiroMiyashita YoheiTakashima SeijiMorita HiroshiIshikawa TaisukeMakita NaomasaHitosugi MasahitoMatsuura HiroshiOhno SeikoHorie MinoruOgita Hisakazu - Human glioblastoma multiforme (GBM) accounts for the majority of human brain gliomas. Several TMEM proteins, such as TMEM 45A, TMEM 97, and TMEM 140, are implicated in human brain gliomas. However, the roles of TMEM168 in human GBM remain poorly understood. Herein we found that mRNA levels of TMEM168 were overexpressed in GBM patients ( = 85) when compared with healthy people ( = 10), which was also supported by data from The Cancer Genome Atlas (TCGA). Kaplan-Meier analysis of Gene Expression Omnibus dataset GSE16011 suggested that enhanced TMEM168 expression was associated with shorter survival time. To investigate whether and how TMEM168 functioned in the tumorigenesis of human GBM cells, two human GBM cell lines (U87 and U373) were used for study. Lithium chloride (LiCl), an activator for Wnt/β-catenin pathway, was used for the treatment. Our data suggested that siRNA-TMEM168 (siTMEM168) prevented viability of U87 and U373 cells, induced cell cycle arrest (G/G phase) and promoted apoptosis, and the mechanisms involved in blocking Wnt/β-catenin pathway, as evidenced by reducing expression of β-catenin, C-myc, cyclin D1, and survivin. Furthermore, the inhibited effect of siTMEM168 on human GBM cell growth was significantly alleviated with additional LiCl treatment, substantiating the involvement of the Wnt/β-catenin pathway in this process. In summary, our data demonstrated that TMEM168 may represent a therapeutic target for the treatment of human GBM. - Source: PubMed
Publication date: 2019/03/25
Xu JieSu ZhongzhouDing QiupingShen LiangNie XiaohuPan XuyanYan AiYan RenfuZhou YueLi LiqinLu Bin - Transmembrane protein 168 (TMEM168) comprises 697 amino acid residues, including some putative transmembrane domains. It is reported that TMEM168 controls methamphetamine (METH) dependence in the nucleus accumbens (NAc) of mice. Moreover, a strong link between METH dependence-induced adaptive changes in the brain and mood disorders has been evaluated. In the present study, we investigated the effects of accumbal TMEM168 in a battery of behavioral paradigms. The adeno-associated virus (AAV) Tmem168 vector was injected into the NAc of C57BL/6J mice (NAc-TMEM mice). Subsequently, the accumbal TMEM168 mRNA was increased approximately by seven-fold when compared with the NAc-Mock mice (controls). The NAc-TMEM mice reported no change in the locomotor activity, cognitive ability, social interaction, and depression-like behaviors; however, TMEM168 overexpression enhanced anxiety in the elevated-plus maze and light/dark box test. The increased anxiety was reversed by pretreatment with the antianxiety drug diazepam (0.3 mg/kg i.p.). Moreover, the NAc-TMEM mice exhibited decreased prepulse inhibition (PPI) in the startle response test, and the induced schizophrenia-like behavior was reversed by pretreatment with the antipsychotic drug risperidone (0.01 mg/kg i.p.). Furthermore, accumbal TMEM168 overexpression decreased the basal levels of extracellular GABA in the NAc and the high K+ (100 mM)-stimulated GABA elevation; however, the total contents of GABA in the NAc remained unaffected. These results suggest that the TMEM168-regulated GABAergic neuronal system in the NAc might become a novel target while studying the etiology of anxiety and sensorimotor gating deficits. - Source: PubMed
Publication date: 2017/12/06
Fu KequanMiyamoto YoshiakiSumi KazuyukiSaika ErikoMuramatsu Shin-IchiUno KyosukeNitta Atsumi