The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components....The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components.The transmembrane protein-39(TMEM-39)mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles.TMEM-39 primarily co-localizes with the coat protein II complex(COPII)in large vesicles rather than small COPII vesicles.These TMEM-39-associated large vesicles(TMEM-39-LVs)form robustly during the molting period and co-localize with various extracellular matrix components,including BLI-1 collagen,BLI-3 dual oxidase,and carboxypeptidases.Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells,we identify TMEM39A-associated proteins,including TMEM131.Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C.elegans and human sarcoma cells,indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles.Given the conservation of TMEM39A and its associated proteins between C.elegans and humans,TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.展开更多
TMEM43基因编码的跨膜蛋白43(transmembrane protein 43,TMEM43)是TMEM蛋白家族成员之一,该蛋白质约为400个氨基酸,包括4个跨膜结构域和1个膜内结构域。TMEM43在许多物种中都存在表达,并且遗传相似性很高,特别是4个跨膜结构在不同物种...TMEM43基因编码的跨膜蛋白43(transmembrane protein 43,TMEM43)是TMEM蛋白家族成员之一,该蛋白质约为400个氨基酸,包括4个跨膜结构域和1个膜内结构域。TMEM43在许多物种中都存在表达,并且遗传相似性很高,特别是4个跨膜结构在不同物种中都表现为高度保守。近年来有研究者发现,TMEM43与听神经病谱系障碍(auditory neuropathy spectrum disorder,ANSD)的发生可能相关,推测其可能为一种新的听力损伤相关基因。本文就现阶段TMEM43基因与听力损伤的关系展开综述,分析TMEM43在耳发育与声传导方面的作用,探讨TMEM43基因变异对听力损伤产生的影响,以期为TMEM43后续研究和精准医疗提供新思路。展开更多
TMEM (Transmembrane, TMEM)是一类整合性膜蛋白,其特点在于能够跨越整个脂质双分子层并永久地锚定其中,分布在线粒体、内质网、溶酶体以及高尔基体等细胞器的细胞膜上。在恶性肿瘤的形成、发展和扩散等关键生物学过程中,TMEM家族蛋白...TMEM (Transmembrane, TMEM)是一类整合性膜蛋白,其特点在于能够跨越整个脂质双分子层并永久地锚定其中,分布在线粒体、内质网、溶酶体以及高尔基体等细胞器的细胞膜上。在恶性肿瘤的形成、发展和扩散等关键生物学过程中,TMEM家族蛋白扮演着举足轻重的角色。这些蛋白质的作用不仅局限于肿瘤细胞的增殖、侵袭和迁移,而且还显示出成为新型肿瘤生物标记物和治疗目标的巨大潜力。本文将对TMEM蛋白在恶性肿瘤研究领域内的最新进展进行回顾和分析。TMEM (Transmembrane, TMEM) is a class of integrated membrane proteins that span and permanently anchor the entire lipid bilayer and are distributed on the cell membranes of organelles such as mitochondria, endoplasmic reticulum, lysosomes and Golgi apparatus. TMEM family proteins play an important role in the formation, development and spread of malignant tumors. The role of these proteins is not limited to the proliferation, invasion and migration of tumor cells, but also shows great potential as novel tumor biomarkers and therapeutic targets. This article will review and analyze the latest progress of TMEM protein in the field of malignant tumor research.展开更多
Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A;p. Ala632Thr) in a 7-year-old boy exhibi...Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A;p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca2+ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^(−/−) OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^(−/−) OPCs in vitro and myelination in Tmem63a^(−/−) mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca^(2+) influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.展开更多
据Sen L 2025年7月11日[Sci Adv,2025,11(28):eads4371-eads4371.]报道,瑞典卡罗林斯卡研究所、法国蒙多尔生物医学研究所和荷兰因兰特大学的研究人员发现了一种称为TMEM9B-AS1的分子,是一种长链非编码RNA(lncRNA),在调节细胞功能中发...据Sen L 2025年7月11日[Sci Adv,2025,11(28):eads4371-eads4371.]报道,瑞典卡罗林斯卡研究所、法国蒙多尔生物医学研究所和荷兰因兰特大学的研究人员发现了一种称为TMEM9B-AS1的分子,是一种长链非编码RNA(lncRNA),在调节细胞功能中发挥重要作用。这一发现可能解释了为什么2型糖尿病患者经常出现肌肉无力和肌肉流失这一影响生活质量和整体健康的原因。展开更多
Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims...Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims to investigate the potential role of Transmembrane protein 33(TMEM33)in the development of lung adenocarcinoma.Methods:We leveraged The Cancer Genome Atlas(TCGA)database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma(LUAD).Cell proliferation,invasiveness,and sphere formation were analyzed by various experiments.The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay,immunoblotting,and real-time quantitative PCR(RT-qPCR).Additionally,TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.Results:TMEM33 showed high expression within both LUAD tissues and cells,with its expression correlating with poor patient survival outcomes.Silencing TMEM33 resulted in significant reductions in cell proliferation,invasiveness,and stem-like properties.Further investigation suggested that miR-214-3p negatively regulated TMEM33.In both cellular and animal models,we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells,impeding tumor growth and inhibiting metastasis in the mouse model.Moreover,reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway,providing insights into TMEM33’s mechanistic role in LUAD.Conclusion:TMEM33 functions as an oncogene,which is under the negative regulation of miR-214-3p,to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.展开更多
基金supported by the National Institutes of Health-Office of Research Infrastructure Programs(P40 OD010440)supported in part by grants from the National Cancer Center of Korea(NCC-2110160,NCC-2110263,and NCC-2310750)supported by the Basic Science Research Program of the National Research Foundation of Korea,funded by the Ministry of Science,ICT,and Future Planning(NRF-2015R1C1A1A01053611).
文摘The growth of Caenorhabditis elegans involves multiple molting processes,during which old cuticles are shed and new cuticles are rapidly formed.This process requires the regulated bulk secretion of cuticle components.The transmembrane protein-39(TMEM-39)mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles.TMEM-39 primarily co-localizes with the coat protein II complex(COPII)in large vesicles rather than small COPII vesicles.These TMEM-39-associated large vesicles(TMEM-39-LVs)form robustly during the molting period and co-localize with various extracellular matrix components,including BLI-1 collagen,BLI-3 dual oxidase,and carboxypeptidases.Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells,we identify TMEM39A-associated proteins,including TMEM131.Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C.elegans and human sarcoma cells,indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles.Given the conservation of TMEM39A and its associated proteins between C.elegans and humans,TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.
文摘TMEM (Transmembrane, TMEM)是一类整合性膜蛋白,其特点在于能够跨越整个脂质双分子层并永久地锚定其中,分布在线粒体、内质网、溶酶体以及高尔基体等细胞器的细胞膜上。在恶性肿瘤的形成、发展和扩散等关键生物学过程中,TMEM家族蛋白扮演着举足轻重的角色。这些蛋白质的作用不仅局限于肿瘤细胞的增殖、侵袭和迁移,而且还显示出成为新型肿瘤生物标记物和治疗目标的巨大潜力。本文将对TMEM蛋白在恶性肿瘤研究领域内的最新进展进行回顾和分析。TMEM (Transmembrane, TMEM) is a class of integrated membrane proteins that span and permanently anchor the entire lipid bilayer and are distributed on the cell membranes of organelles such as mitochondria, endoplasmic reticulum, lysosomes and Golgi apparatus. TMEM family proteins play an important role in the formation, development and spread of malignant tumors. The role of these proteins is not limited to the proliferation, invasion and migration of tumor cells, but also shows great potential as novel tumor biomarkers and therapeutic targets. This article will review and analyze the latest progress of TMEM protein in the field of malignant tumor research.
基金supported by grants from the National Key R&D Program of China(2019YFA0801603)the Guangdong High Level Innovation Research Institute(2021B0909050004)+2 种基金the National Natural Science Foundation of China(32330044,32170951,82201615,and 82101393)the Natural Science Foundation of Jiangsu Province(BK20201255 and BK20210008)the Fundamental Research Funds for the Central Universities(021414380533).
文摘Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A;p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca2+ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^(−/−) OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^(−/−) OPCs in vitro and myelination in Tmem63a^(−/−) mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca^(2+) influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
文摘据Sen L 2025年7月11日[Sci Adv,2025,11(28):eads4371-eads4371.]报道,瑞典卡罗林斯卡研究所、法国蒙多尔生物医学研究所和荷兰因兰特大学的研究人员发现了一种称为TMEM9B-AS1的分子,是一种长链非编码RNA(lncRNA),在调节细胞功能中发挥重要作用。这一发现可能解释了为什么2型糖尿病患者经常出现肌肉无力和肌肉流失这一影响生活质量和整体健康的原因。
文摘Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims to investigate the potential role of Transmembrane protein 33(TMEM33)in the development of lung adenocarcinoma.Methods:We leveraged The Cancer Genome Atlas(TCGA)database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma(LUAD).Cell proliferation,invasiveness,and sphere formation were analyzed by various experiments.The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay,immunoblotting,and real-time quantitative PCR(RT-qPCR).Additionally,TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.Results:TMEM33 showed high expression within both LUAD tissues and cells,with its expression correlating with poor patient survival outcomes.Silencing TMEM33 resulted in significant reductions in cell proliferation,invasiveness,and stem-like properties.Further investigation suggested that miR-214-3p negatively regulated TMEM33.In both cellular and animal models,we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells,impeding tumor growth and inhibiting metastasis in the mouse model.Moreover,reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway,providing insights into TMEM33’s mechanistic role in LUAD.Conclusion:TMEM33 functions as an oncogene,which is under the negative regulation of miR-214-3p,to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.
