更新于：2024-09-19

RAB13

更新于：2024-09-19

基本信息

别名

Cell growth-inhibiting gene 4 protein、RAB13、RAB13, member RAS oncogene family

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简介

The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in endocytic recycling and regulates the transport to the plasma membrane of transmembrane proteins like the tight junction protein OCLN/occludin. Thereby, it regulates the assembly and the activity of tight junctions. Moreover, it may also regulate tight junction assembly by activating the PKA signaling pathway and by reorganizing the actin cytoskeleton through the activation of the downstream effectors PRKACA and MICALL2 respectively. Through its role in tight junction assembly, may play a role in the establishment of Sertoli cell barrier. Plays also a role in angiogenesis through regulation of endothelial cells chemotaxis. Also involved in neurite outgrowth. Has also been proposed to play a role in post-Golgi membrane trafficking from the TGN to the recycling endosome. Finally, it has been involved in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore may play a role in glucose homeostasis.

关联

100 项与 RAB13 相关的临床结果

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100 项与 RAB13 相关的转化医学

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0 项与 RAB13 相关的专利（医药）

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128

项与 RAB13 相关的文献（医药）

2024-09-01·International Immunopharmacology

4D label-free proteomic analysis reveals key potential pathways of Toxoplasma invasion into the central nervous system

Article

作者: Yuan, Zi-Guo ; Nie, Linchong ; Ren, Zhaowen ; Yang, Zipeng ; Wang, Xiaohu ; Zhang, Xiu-Xiang ; He, Houjing ; Song, Yining ; Yuan, Hao

Toxoplasma gondii is a successful parasite capable of infecting a wide range of warm-blooded animals, including people, livestock, and wildlife. In individuals with intact immune function, T. gondii can invade the host brain tissue by altering the blood-brain barrier permeability, leading to chronic infection. Proteins play crucial regulatory roles in disease progression. By monitoring changes in proteins, a deeper understanding of the molecular mechanisms underlying host resistance to infection and the potential pathogenic mechanisms of pathogens can be gained. This study analyzed differential protein expression and associated signaling pathways in mouse brain tissues during acute and chronic T. gondii infection using proteomic and bioinformatics methods. The results showed that during acute and chronic T. gondii infection stages, 74 and 498 differentially expressed proteins (DEPs) were identified in mouse brain tissue, respectively. Among them, 45 and 309 were up-regulated, while 29 and 189 were down-regulated. GO and KEGG analyses revealed that some of these DEPs were implicated in host immunity, pathogen immune evasion, and T. gondii invasion of the central nervous system, particularly interleukin production and secretion, complement system activation, and alterations in tight junction pathways. Notably, the upregulation of Rab13 was identified as a potential molecular mechanism for T. gondii to regulate blood-brain barrier permeability and facilitate central nervous system invasion. Our findings provided fundamental data for understanding host control of Toxoplasmosis infection and offered new insights into parasite immune evasion and invasion mechanisms within the central nervous system. These insights are crucial for developing strategies to prevent the establishment of chronic T. gondii infection.

2024-01-01·Bioengineering & Translational Medicine

Sound conditioning strategy promoting paracellular permeability of the blood‐labyrinth‐barrier benefits inner ear drug delivery

Article

作者: Xu, Baoying ; Wu, Hao ; Xu, Ke ; Yu, Dehong ; Gu, Jiayi ; Wang, Xueling

AbstractThe therapeutic effects of pharmaceuticals depend on their drug concentrations in the cochlea. Efficient drug delivery from the systemic circulation into the inner ear is limited by the blood‐labyrinth‐barrier (BLB). This study investigated a novel noninvasive sound conditioning (SC) strategy (90 dB SPL, 8–16 kHz, 2 h sound exposure) to temporally enhance BLB permeability in a controllable way, contributing to maximizing the penetration of pharmaceuticals from blood circulation into the cochlea. Trafficking of Fluorescein Isothiocyanate conjugated dextran and bovine serum albumin (FITC‐dextran and FITC‐BSA) demonstrated that paracellular leakage of BLB sustained for 6 h after SC, providing a controllable time window for systemic administration. Cochlear concentrations of dexamethasone (DEX) and dexamethasone phosphate (DEX‐P), respectively transported by transcellular and paracellular pathways, showed a higher content of the latter one after SC, further confirming the key role of paracellular pathway in the SC‐induced hyperpermeability. Results of high‐throughput RNA‐sequencing identified a series of tight junction (TJ)‐associated genes after SC. The expressions of TJ (ZO‐1) were reduced and irregular rearrangements of the junction were observed by transmission electron microscopy after SC. We further determined the inhibiting role of Rab13 in the recruitment of ZO‐1 and later in the regulation of cellular permeability. Meanwhile, no significant change in the quantifications of endothelial caveolae vesicles after SC indicated that cellular transcytosis accounted little for the temporary hyperpermeability after SC. Based on these results, SC enhances the BLB permeability within 6 h and allows systemically applied drugs which tend to be transported by paracellular pathway to readily enter the inner ear, contributing to guiding the clinical medications on hearing loss.

2023-09-18·ACS applied bio materials

A Fluorescent Vector of Carbon Dot to Deliver Rab13 and Rab14 Plasmids for Promoting Neurite Outgrowth.

Article

作者: Huang, Yung-Chin ; Wang, Po-Hsiang ; Chien, Fan-Ching ; Lin, Tzu-Chau ; Luo, Ching-Lung ; Chuang, Chia-Cheng ; Lai, Jian-Zong

The complex processes of neuron differentiation and neuron repair are critical for treating nervous system injuries and neurodegenerative diseases. Neurite outgrowth plays a crucial role in these processes by enabling the formation of connections between neurons and the generation of neuroplasticity to restore the function of the nervous system. In this study, we fabricated functionalized carbon dots (CDs) with distinctive photoluminescence and low cytotoxicity for use as fluorescence imaging probes and nanocarriers to deliver plasmid DNAs to neurons effectively for inducing neurite outgrowth. CDs were prepared through a reflux process in nitric acid solution, and their surface was then modified using polyethylenimine (PEI) to obtain positively charged CDs for increasing the absorption of plasmid DNAs and the efficiency of cell uptake. Experimental results indicated that the fabricated CDs maintained a low cytotoxicity and exhibited a high neuron uptake of up to 97%. An improvement in the plasmid DNA ingestion of neurons resulted in enhanced expression of Rab13-Q67L and Rab14 proteins, which considerably promoted neurite sprouting and elongation. After the fabricated PEI-modified CDs were used to deliver the Rab13-Q67L and Rab14 plasmids, more than 56% of the neurons had a neurite length that was greater than twice the size of their soma. Thus, DNA delivery through functionalized CDs has a high potential for use in gene therapy for neuronal injuries and diseases.

项与 RAB13 相关的新闻（医药）

2024-01-30

·生物探索

CMI | 武汉大学林丹丹/钟波/陈小奇发现双硫仑通过靶向RNF115改善STING/MITA依赖性炎症和自身免疫

引言STING(也称为MITA)是一种介导细胞质DNA触发信号的接头蛋白，细胞质自身DNA或功能获得突变异常激活STING/MITA会导致严重的炎症。2024年1月24日，武汉大学林丹丹、钟波及陈小奇共同通讯在Cellular & Molecular Immunology（IF 24）在线发表题为“Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115”的研究论文，该研究发现STING介导的炎症和自身免疫可由RNF115促进，并可由RNF115抑制剂双硫仑(DSF)缓解。在Trex1-/-小鼠和STINGN153S/WT骨髓嵌合小鼠中，敲除RNF115或用DSF治疗可显著抑制全身炎症和自身免疫致死性，恢复免疫细胞发育。此外，RNF115的敲低或药理抑制可显著下调外周血中dsDNA浓度较高的系统性红斑狼疮(SLE)患者外周血中IFN-α、IFN-γ和促炎细胞因子的表达。从机制上讲，敲除或抑制RNF115会损害转染cGAMP的各种类型的细胞以及Trex1-/-小鼠的器官和细胞中STING的寡聚化和高尔基体定位。有趣的是，敲除RNF115会抑制髓细胞中STINGN153S的激活和高尔基定位以及促炎细胞因子的表达，而内皮细胞和成纤维细胞则不会。这些发现突出了RNF115介导的STING和STINGN153S的细胞类型特异性调控，并为STING相关自身免疫性疾病提供了潜在的靶向干预策略。在稳态条件下，宿主DNA被隔离在细胞核或线粒体中。在应激条件下，核DNA或线粒体DNA (mtDNA)渗漏到细胞质中并在细胞质中积累，或者在DNA酶II和TREX1等基因突变的作用下，激活cGAS-cGAMP-STING轴，诱发严重炎症。例如，TREX1是一种降解自身DNA的DNA外切酶，TREX1的功能丧失突变与人类自身免疫性疾病密切相关，如Aicardi-Goutieres综合征(AGS)、视网膜血管病变伴脑白质营养不良(RVCL)和系统性红斑狼疮(SLE)。TREX1的功能缺失突变或敲除导致细胞质中自身DNA的积累和cGAS-cGAMP-STING通路的持续激活，从而引发自身免疫反应。因此，Trex1-/-和TREX1D18N小鼠会出现严重的全身性炎症，并表现出致命的自身免疫，这种免疫可以通过STING的缺失在基因上得到拯救，这表明STING在由自身DNA引起的自身免疫性疾病中发挥着重要作用。除了胞质DNA外，STING的功能获得突变(其中最常见的是STINGN154s和STING V155M)介导下游信号通路的激活，导致一种称为STING的自身免疫性疾病，与婴儿期发病相关的血管病变(SAVI)。SAVI患者表现为全身性炎症、间质性肺疾病、外周血单个核细胞(PBMCs)中IFN产生和ISG特征表达旺盛。在小鼠模型中，携带STINGN153S或STINGV154M突变(分别与人类STINGN154S或STINGV155M同源)的杂合敲入小鼠表现出骨髓细胞扩增、T细胞减少、肺部炎症和过早死亡。激活功能性NF-κB途径和炎症基因特征，而不是激活IRF3途径，在STINGN153S小鼠中起主导作用，因为在STINGN153S小鼠中删除IRF3、IRF7或IFNR1不能挽救致命的自身免疫表型。在机制上，在缺乏cGAMP的情况下，获得功能的STING突变体会自发和组成性地从内质网转移到高尔基体，从而触发炎症细胞因子的诱导。然而，STING的功能获得突变体是否需要翻译后修饰来实现其自发的ER-to-Golgi易位以及相关的潜在机制尚不清楚。因此，破译STING激活的调控机制和靶向活化的STING将为理解自身免疫和开发自身免疫性疾病的潜在治疗策略提供见解。抑制RNF115可下调SLE患者外周血细胞中促炎细胞因子的表达（Credit: Cellular & Molecular Immunology）RNF115参与乳腺癌、肺腺癌和胃癌的肿瘤发生和恶性细胞的迁移。最近报道，RNF115通过催化RAB1A和RAB13的泛素化并抑制它们与鸟苷二磷酸(GDP)解离抑制剂(GDI)的相互作用来抑制TLRs的再激活，从而负性介导内质网和高尔基体后TLRs的转运。还证明，RNF115通过催化MAVS的泛素化，构成性地破坏MAVS的稳定。相反，RNF115介导STING的k63连锁泛素化，促进其在HSV-1感染后的寡聚、运输和活化。然而，在自发性炎症的情况下，RNF115是否调控STING的活性，以及其潜在的机制仍有待研究。该研究报道RNF115是一种E3连接酶，在Trex1-/- 细胞和组织中与STING相互作用。RNF115通过催化STING或STINGN153S的k63连锁泛素化来促进STING介导的炎症和自身免疫，该泛素化被RNF115抑制剂双硫醚(DSF)减弱。RNF115的缺失或药理抑制可减弱Trex1-/-小鼠和STINGN153S/WT骨髓嵌合小鼠的自身免疫表型。此外，敲除RNF115或用DSF治疗显著下调外周血dsDNA浓度高的SLE患者外周血PBMCs中IFN-α、IFN-γ和促炎细胞因子的表达。从机制上讲，敲除或抑制RNF115会损害TREX1缺陷小鼠细胞和器官中与K63相关的STING泛素化和寡聚化，并抑制髓细胞中STINGN153S的高尔基定位。该研究结果强调了STING受RNF115调控作为自身免疫性疾病治疗干预靶点的过程。原文链接https://www-nature-com.libproxy1.nus.edu.sg/articles/s41423-024-01131-3责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Science最新发布：全世界最前沿的125个科学问题热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文Nature | 新一代肥胖药物的双重威力：抑制炎症与治疗帕金森及阿尔茨海默症的希望