Ask about this productRelated genes to: TRAPPC6B antibody
- Gene:
- TRAPPC6B NIH gene
- Name:
- trafficking protein particle complex 6B
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 14q21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-09-01
- Date modifiied:
- 2016-10-05
Related products to: TRAPPC6B antibody
Related articles to: TRAPPC6B antibody
- Tuberculosis, caused by (Mtb) infection, remains one of the most deadly infectious diseases worldwide. There is an urgent need for the development of innovative strategies improving the antibiotic efficiency and enhancing host immunological defenses for more effective TB treatment. CircRNA TRAPPC6B (circTRAPPC6B) can enhance autophagy and M1 polarization of Mtb infected macrophages to facilitate intracellular Mtb clearance, arising the promise for more effective anti-TB treatment. Here, we innovated macrophage targeted cellular microparticles encapsulating circTRAPPC6B and rifampicin inside to synergize targeted drug killing and enhanced host immunological clearance, thereby providing more effective anti-TB treatment to optimize therapeutic outcomes. The engineered Gal-CircRNA@Rif@MPs nanosystem showed selective macrophage targeting effects due to galacose surface functionalization and could significantly increase intracellular circTRAPPC6B levels, thereby promoting autophagy and anti-bacterial polarization of Mtb infected macrophages. Collectively, Gal-CircRNA@Rif@MPs demonstrated enhanced intracellular Mtb killing efficiency by synergizing targeted rifampicin action and antibacterial host immune defenses, thus significantly reducing Mtb burdens and alleviating lung tissue pathology in Mtb-infected mice without notable toxicity. Our findings demonstrate, for the first time, that circRNAs with immunomodulatory properties can be effectively combined with anti-TB drugs using cellular microparticles to achieve host cell-targeted Mtb clearance with alleviated pathology and acceptable toxicity profiles. These results introduce the potentials of Gal-CircRNA@Rif@MPs as novel host cell targeted system to synchronize selective antibiotic actions and host immunological defenses for more effective anti-TB treatment, advancing novel therapeutics against TB. - Source: PubMed
Publication date: 2025/10/29
Ma YuheYang FenLiu JuanZhao YiHuang YuheWang JiajunLi JiaxiangKong XinenJin XiaoyingLin SiqiChen LingmingZhao XiaoleiZhao DainaHuang XueqinGong HaiyanShen LingCong YanguangLiu XingXu Jun-FaPi Jiang - Tuberculosis (TB), a highly lethal infectious diseases induced by Mycobacterium tuberculosis (Mtb) infection, continues to be a major challenge in the realm of infectious diseases. Functional circular RNAs (circRNAs) have been extensively reported to play crucial immunological regulatory roles in Mtb infection and TB development. Our previous researches have demonstrated that CircRNA TRAPPC6B (circTRAPPC6B) can enhance autophagy in Mtb infected macrophages to facilitate intracellular Mtb inhibition/clearance, while how to expand the potential of circTRAPPC6B for effective anti-TB treatment remains a considerable challenge. Here, we innovated a novel macrophage-targeted exosome system, designated as Man-Rif@CircRNA@Exo, which encapsulates circTRAPPC6B and rifampicin to synchronize targeted antibiotic killings and host immunological defenses against Mtb. Man-Rif@CircRNA@Exo exhibited selective macrophage targeting effects attributable to mannose modification and then accumulated into lysosomes of macrophages. Furthermore, Man-Rif@CircRNA@Exo treatment significantly increased intracellular circTRAPPC6B level, which in turn promoted autophagy of Mtb infected macrophages, thereby accelerating host immunological clearance of Mtb. Collectively, Man-Rif@CircRNA@Exo indicated enhanced intracellular Mtb killing efficiency by synergizing targeted rifampicin bacteriocidal action with autophagy-mediated host immunological clearance against Mtb. This synergistic anti-TB approach significantly reduced Mtb burdens and alleviated tissue pathology and inflammation in the lungs of Mtb-infected mice, without significantly affecting liver/kidney structure and functional parameters to show acceptable safety. These results highlight the promising potential of Man-Rif@CircRNA@Exo to synchronize targeted antibiotic action and host immunological defenses for more effective anti-TB treatment, which is anticipated to advance the development of novel host directed therapeutics against TB and drug-resistant TB. - Source: PubMed
Publication date: 2025/10/24
Pi JiangMa YuheWang WandangHuang HuanshaoHuang YuheWang JiajunLi JiaxiangKong XinenJin XiaoyingLiu ShengCai JialiCong YanguangGong HaiyanShen LingHuang YifanHuang XueqinXu Jun-Fa - To explore the clinical phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease. - Source: PubMed
Li WenxiaLi YukeChen BaiyunLi WeimengZhang XiaomanLi LinfeiShang Qing - Variants in membrane trafficking proteins are known to cause rare disorders with severe symptoms. The highly conserved transport protein particle (TRAPP) complexes are key membrane trafficking regulators that are also involved in autophagy. Pathogenic genetic variants in specific TRAPP subunits are linked to neurological disorders, muscular dystrophies, and skeletal dysplasias. Characterizing these variants and their phenotypes is important for understanding the general and specialized roles of TRAPP subunits as well as for patient diagnosis. Patient-derived cells are not always available, which poses a limitation for the study of these diseases. Therefore, other systems, like the yeast , can be used to dissect the mechanisms at the intracellular level underlying these disorders. The development of CRISPR/Cas9 technology in yeast has enabled a scar-less editing method that creates an efficient humanized yeast model. In this study, core yeast subunits were humanized by replacing them with their human orthologs, and TRAPPC1, TRAPPC2, TRAPPC2L, TRAPPC6A, and TRAPPC6B were found to successfully replace their yeast counterparts. This system was used for studying the first reported individual with an autosomal recessive disorder caused by biallelic variants, a girl with a severe neurodevelopmental disorder and myopathy. We show that the maternal variant (TRAPPC1 p.(Val121Alafs*3)) is non-functional while the paternal variant (TRAPPC1 p.(His22_Lys24del)) is conditional-lethal and affects secretion and non-selective autophagy in yeast. This parallels defects seen in fibroblasts derived from this individual which also showed membrane trafficking defects and altered Golgi morphology, all of which were rescued in the human system by wild-type . This study suggests that humanized yeast can be an efficient means to study TRAPP subunit variants in the absence of human cells and can assign significance to variants of unknown significance (VUS). This study lays the foundation for characterizing further TRAPP variants through this system, rapidly contributing to disease diagnosis. - Source: PubMed
Publication date: 2024/08/30
Zykaj ErtaAbboud ChelseaAsadi PariaWarsame SimaneAlmousa HashemMilev Miroslav PGreco Brittany MLópez-Sánchez MarcosBratkovic DragoKachroo Aashiq HPérez-Jurado Luis AlbertoSacher Michael - Highly conserved transport protein particle (TRAPP) complexes regulate subcellular trafficking pathways. Accurate protein trafficking has been increasingly recognized to be critically important for normal development, particularly in the nervous system. Variants in most TRAPP complex subunits have been found to lead to neurodevelopmental disorders with diverse but overlapping phenotypes. We expand on limited prior reports on TRAPPC6B with detailed clinical and neuroradiologic assessments, and studies on mechanisms of disease, and new types of variants. We describe 29 additional patients from 18 independent families with biallelic variants in TRAPPC6B. We identified seven homozygous nonsense (n = 12 patients) and eight canonical splice-site variants (n = 17 patients). In addition, we identified one patient with compound heterozygous splice-site/missense variants with a milder phenotype and one patient with homozygous missense variants. Patients displayed non-progressive microcephaly, global developmental delay/intellectual disability, epilepsy and absent expressive language. Movement disorders including stereotypies, spasticity and dystonia were also observed. Brain imaging revealed reductions in cortex, cerebellum and corpus callosum size with frequent white matter hyperintensity. Volumetric measurements indicated globally diminished volume rather than specific regional losses. We identified a reduced rate of trafficking into the Golgi apparatus and Golgi fragmentation in patient-derived fibroblasts that was rescued by wild-type TRAPPC6B. Molecular studies revealed a weakened interaction between mutant TRAPPC6B (c.454C>T, p.Q152*) and its TRAPP binding partner TRAPPC3. Patient-derived fibroblasts from the TRAPPC6B (c.454C>T, p.Q152*) variant displayed reduced levels of TRAPPC6B as well as other TRAPP II complex-specific members (TRAPPC9 and TRAPPC10). Interestingly, the levels of the TRAPPC6B homologue TRAPPC6A were found to be elevated. Moreover, co-immunoprecipitation experiments showed that TRAPPC6A co-precipitates equally with TRAPP II and TRAPP III, while TRAPPC6B co-precipitates significantly more with TRAPP II, suggesting enrichment of the protein in the TRAPP II complex. This implies that variants in TRAPPC6B may preferentially affect TRAPP II functions compared to TRAPP III functions. Finally, we assessed phenotypes in a Drosophila TRAPPC6B-deficiency model. Neuronal TRAPPC6B knockdown impaired locomotion and led to wing posture defects, supporting a role for TRAPPC6B in neuromotor function. Our findings confirm the association of damaging biallelic TRAPPC6B variants with microcephaly, intellectual disability, language impairments, and epilepsy. A subset of patients also exhibited dystonia and/or spasticity with impaired ambulation. These features overlap with disorders arising from pathogenic variants in other TRAPP subunits, particularly components of the TRAPP II complex. These findings suggest that TRAPPC6B is essential for brain development and function, and TRAPP II complex activity may be particularly relevant for mediating this function. - Source: PubMed
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