更新于：2024-09-19

GOSR1

更新于：2024-09-19

基本信息

别名

28 kDa cis-Golgi SNARE p28、28 kDa Golgi SNARE protein、golgi SNAP receptor complex member 1

+ [6]

简介

Involved in transport from the ER to the Golgi apparatus as well as in intra-Golgi transport. It belongs to a super-family of proteins called t-SNAREs or soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor. May play a protective role against hydrogen peroxide induced cytotoxicity under glutathione depleted conditions in neuronal cells by regulating the intracellular ROS levels via inhibition of p38 MAPK (MAPK11, MAPK12, MAPK13 and MAPK14). Participates in docking and fusion stage of ER to cis-Golgi transport. Plays an important physiological role in VLDL-transport vesicle-Golgi fusion and thus in VLDL delivery to the hepatic cis-Golgi.

关联

100 项与 GOSR1 相关的临床结果

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100 项与 GOSR1 相关的转化医学

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0 项与 GOSR1 相关的专利（医药）

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项与 GOSR1 相关的文献（医药）

2023-08-01·Traffic (Copenhagen, Denmark)

Syntaxin-5's flexibility in SNARE pairing supports Golgi functions.

Article

作者: D'Souza, Zinia ; Pokrovskaya, Irina ; Lupashin, Vladimir V

Deficiency in the conserved oligomeric Golgi (COG) complex that orchestrates SNARE-mediated tethering/fusion of vesicles that recycle the Golgi's glycosylation machinery results in severe glycosylation defects. Although two major Golgi v-SNAREs, GS28/GOSR1, and GS15/BET1L, are depleted in COG-deficient cells, the complete knockout of GS28 and GS15 only modestly affects Golgi glycosylation, indicating the existence of an adaptation mechanism in Golgi SNARE. Indeed, quantitative mass-spectrometry analysis of STX5-interacting proteins revealed two novel Golgi SNARE complexes-STX5/SNAP29/VAMP7 and STX5/VTI1B/STX8/YKT6. These complexes are present in wild-type cells, but their usage is significantly increased in both GS28- and COG-deficient cells. Upon GS28 deletion, SNAP29 increased its Golgi residency in a STX5-dependent manner. While STX5 depletion and Retro2-induced diversion from the Golgi severely affect protein glycosylation, GS28/SNAP29 and GS28/VTI1B double knockouts alter glycosylation similarly to GS28 KO, indicating that a single STX5-based SNARE complex is sufficient to support Golgi glycosylation. Importantly, co-depletion of three Golgi SNARE complexes in GS28/SNAP29/VTI1B TKO cells resulted in severe glycosylation defects and a reduced capacity for glycosylation enzyme retention at the Golgi. This study demonstrates the remarkable plasticity in SXT5-mediated membrane trafficking, uncovering a novel adaptive response to the failure of canonical intra-Golgi vesicle tethering/fusion machinery.

2023-02-01·Traffic

Acute COG complex inactivation unveiled its immediate impact on Golgi and illuminated the nature of intra‐Golgi recycling vesicles

Article

作者: D'Souza, Zinia ; Lupashin, Vladimir V. ; Sumya, Farhana Taher ; Pokrovskaya, Irina D.

AbstractConserved Oligomeric Golgi (COG) complex controls Golgi trafficking and glycosylation, but the precise COG mechanism is unknown. The auxin‐inducible acute degradation system was employed to investigate initial defects resulting from COG dysfunction. We found that acute COG inactivation caused a massive accumulation of COG‐dependent (CCD) vesicles that carry the bulk of Golgi enzymes and resident proteins. v‐SNAREs (GS15, GS28) and v‐tethers (giantin, golgin84, and TMF1) were relocalized into CCD vesicles, while t‐SNAREs (STX5, YKT6), t‐tethers (GM130, p115), and most of Rab proteins remained Golgi‐associated. Airyscan microscopy and velocity gradient analysis revealed that different Golgi residents are segregated into different populations of CCD vesicles. Acute COG depletion significantly affected three Golgi‐based vesicular coats—COPI, AP1, and GGA, suggesting that COG uniquely orchestrates tethering of multiple types of intra‐Golgi CCD vesicles produced by different coat machineries. This study provided the first detailed view of primary cellular defects associated with COG dysfunction in human cells.

2023-01-01·Current protein & peptide science

Diverse Role of SNARE Protein GS28 in Vesicle Trafficking and Diseases.

Review

作者: Liu, Rongrong ; Li, Miaomiao ; Zhao, Yaping ; Liu, Pengfei

Golgi SNARE, with a size of 28 kD (GS28), is a transmembrane protein and mainly localizes to the Golgi apparatus. It is considered a core part of the Golgi SNARE complex in the Endoplasmic Reticulum (ER)-Golgi transport and regulates the docking and fusion of transport vesicles effectively. In recent years, increasing studies have indicated that various intracellular transport events are regulated by different GS28-based SNARE complexes. Moreover, GS28 is also involved in numerous functional signaling pathways related to different diseases via interacting with other SNARE proteins and affecting protein maturation and secretion. However, the precise function of GS28 in different disease models and the regulatory network remains unclear. In this review, we mainly provide a concise overview of the function and regulation of GS28 in vesicle trafficking and diseases and summarize the signaling pathways regarding potential mechanisms. Although some critical points about the significance of GS28 in disease treatment still need further investigation, more reliable biotechnical or pharmacological strategies may be developed based on a better understanding of the diverse role of GS28 in vesicle trafficking and other biological processes.

项与 GOSR1 相关的新闻（医药）

2024-01-07

·佰傲谷BioValley

肥胖环境中的免疫细胞

Autoimmunity Reviews脂肪组织(AT)包括内脏脂肪组织(VAT)和皮下脂肪组织(SAT)，是炎症细胞因子的产生来源。AT对炎症和适应性免疫功能均有影响。肥胖会导致促炎免疫细胞(包括巨噬细胞和淋巴细胞)在内脏脂肪组织中积累，这些细胞具有高水平的营养代谢，从而驱动低度炎症，促进代谢疾病。脂肪组织中的免疫细胞B细胞及其抗体主要是致病性IgG抗体的产生。饮食诱导的肥胖小鼠的VAT能观察到B淋巴细胞浸润，产生致病性IgG抗体。这种脂肪细胞特异性IgG抗体的分泌来自肥胖AT中正在进行的脂肪细胞死亡过程，诱导B细胞慢性刺激的“自身”抗原的释放。这一过程无需外源性刺激即可发生。产生的IgG大多集中于VAT的冠状结构区域，由大的单核和多核巨噬细胞以及垂死的脂肪细胞组成，可能参与垂死脂肪细胞的清除。人体中这种B细胞分泌的致病性IgG表达GOSR1、BTK、GFAP和HSP60，前三者与其胰岛素抵抗密切相关，多在细胞内，广泛表达。APC垂死的脂肪细胞会引起针对AT细胞表达的自身抗原的体液反应。脂肪细胞表达抗原呈递细胞（APC）的典型标志物，如CD1d和MHCII。根据自身抗体的抗原特异性进行表征，然后根据抗原的细胞位置(近一半是细胞质)和抗原参与的生物学过程(主要是代谢过程)进行分类。DC：是肥胖小鼠和人体AT中积累的主要APC，诱导Th17细胞分化。相比正常DC，肥胖组织中DC表达CD40、CD80、CD86和MHC的水平均偏低。缺乏CD40和体重增加、胰岛素抵抗程度有关。此外，传统的ATDC还表达CD11c+ CD64-，并依赖CCR7在高脂饮食环境中增殖和积累。巨噬细胞：CD40是DC和巨噬细胞共同表达的一个影响因素，但是在这两种APC中的水平却截然相反。小鼠模型显示obesity AT中的巨噬细胞高表达CD40。敲除小鼠CD40基因后，巨噬细胞膜上的MHCII和CD86表达减少，但却与胰岛素敏感性的改善无关。这也解释了CD40为什么在AT炎症中有相反的作用。T细胞AT中T细胞表达更多的IFN-γ+ 和GZMB+，能在TCR信号激活时产生更多的炎症介质。CD4+ T细胞能够调控肥胖相关代谢异常，是通过一种不涉及Treg细胞或IL-10而是Th2细胞的机制，来解决脂肪细胞肥大造成的内脏脂肪和胰岛素敏感性等代谢障碍问题。AT中的T细胞亚群比例也和正常组织不同。例如，SAT中幼稚T细胞比例减少，VAT中则增加了效应T细胞和记忆T细胞亚群。Th1/Treg：肥胖AT中整体Treg比例偏低。Th1/Treg比值受到STAT3信号通路的影响。VAT中Treg比例低于SAT，同时Th1细胞则比SAT中的更丰富。高脂饮食可增加VAT中的Th1比例，也就从而增加Th1/Treg比值，BMI与VAT中的Treg数值呈负相关。CD8+ 记忆T细胞：SAT中还存在一组特殊的CD8+ 记忆T细胞，高表达金属硫蛋白基因(MT1E、MT1F、MT1G、MT1X和MT2A)。该亚群能够增加T细胞上IL-2受体的表达，同时抑制T细胞向细胞毒性淋巴细胞分化，从而导致幼稚T细胞比例反而增加，细胞毒性效应T细胞表型则减少。Th17细胞通过产生IL-17促进前脂肪细胞分化和促炎细胞因子产生，造成AT炎症。在VAT中，IL-17通过TBK1介导增加Th1细胞、减少Th2细胞和M2巨噬细胞数量。iNKT细胞iNKT能够识别表达于M2巨噬细胞和脂肪细胞上由CD1d提呈的脂类抗原，对肥胖体重和糖代谢的作用是复杂的。在肥胖的人类和小鼠的AT中观察到，iNKT被耗尽，与促炎巨噬细胞渗透平行增加，并在体重减轻后恢复。积极作用：脂肪滞留的iNKT在肝脏和脾中产生较少的IFN-γ，而产生较多的IL-4和IL-10。阻断IL-4和IL-10的分泌会减弱iNKT激活对改善胰岛素抵抗的作用，但对减轻体重的作用保持不变。iNKT对体重和糖代谢的积极作用包含成纤维细胞生长因子21(FGF-21)的分泌，进而通过上调解偶联蛋白1(UCP1)的表达而诱导白色脂肪组织(WAT)的褐化，以及通过产生IL-2和IL-10而通过Treg和募集以及M2巨噬细胞的极化。负面作用：在另一些小鼠实验中却观察到，肥胖小鼠的AT中iNKT增加，高脂饮食诱导iNKT分泌促炎细胞因子，但不诱导抗炎细胞因子。NK细胞饮食诱导的肥胖小鼠VAT中NK细胞和NK细胞产生的IFN-γ水平均高于瘦小鼠，这是由于肥胖诱导的脂肪细胞表面NK细胞配体上调所致。NK细胞和IFN-γ反过来促进巨噬细胞向促炎M1表型中分化和影响胰岛素抵抗。巨噬细胞在肥胖期间巨噬细胞被招募到VAT和SAT，并且它们的数量与脂肪细胞大小和体重相关。巨噬细胞的浸润与脂肪细胞的脂解和多核巨细胞的形成有关。在与体重增加相关的前100个基因中，有30个基因编码巨噬细胞相关蛋白。瘦小鼠AT中的巨噬细胞主要由M2极化细胞组成；相反，在饮食诱导的肥胖小鼠中，M1/M2比率增加。中性粒细胞、嗜酸性粒细胞、肥大细胞其主要作用是影响巨噬细胞招募和浸润。中性粒细胞通过CD11b和ICAM-1与脂肪细胞相互作用。嗜酸性粒细胞也在AT的巨噬细胞募集中发挥重要作用，作为IL-4的主要来源激活巨噬细胞，诱导其向M2表型分化。肥大细胞通过分泌IL-6和IFN-γ来促进AT中的炎症、细胞凋亡和血管生成，从而导致肥胖和糖耐量减低。肥胖的人类和小鼠的肥大细胞数量比瘦的人更多。肥大细胞膜稳定剂能够改善肥胖小鼠的体重和胰岛素敏感性。Autoimmunity Reviews参考文献：1.Nicola Susca, Patrizia Leone, Marcella Prete, Susanna Cozzio, Vito Racanelli,Adipose failure through adipocyte overload and autoimmunity,Autoimmunity Reviews,Volume 23, Issue 3,2024,103502,ISSN 1568-9972,https://doi-org.libproxy1.nus.edu.sg/10.1016/j.autrev.2023.103502.2.Shaikh, S.R., Beck, M.A., Alwarawrah, Y. et al. Emerging mechanisms of obesity-associated immune dysfunction. Nat Rev Endocrinol (2023). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41574-023-00932-2本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀ ···

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