SNARE

SNARE
  • 文章类型: Journal Article
    沙眼衣原体,细菌性传播感染的主要原因,通过将多种效应子(Incs[包涵膜蛋白])易位并插入包涵膜中,可以创建专门的细胞内复制性小生境。这里,我们描述IncE,一种多功能公司,在其短胞质C末端编码两个不重叠的短线性基序(SLiMs)。近端SLiM,通过模仿R-N-乙基马来酰亚胺敏感因子衔接蛋白受体(SNARE)基序的一小部分,结合并募集含突触素(STX)7-和STX12的囊泡。远端SLiM模拟分选nexin(SNX)5和SNX6货物结合位点,以招募包含SNX6的囊泡。通过同时结合两种不同的囊泡类型,IncE使这些囊泡在包涵体处彼此紧密并置,以促进沙眼衣原体细胞内发育。我们的工作表明,Incs可能已经进化出SLiM,使其能够在有限的蛋白质空间中快速进化,从而破坏宿主细胞过程。
    Chlamydia trachomatis, a leading cause of bacterial sexually transmitted infections, creates a specialized intracellular replicative niche by translocation and insertion of a diverse array of effectors (Incs [inclusion membrane proteins]) into the inclusion membrane. Here, we characterize IncE, a multifunctional Inc that encodes two non-overlapping short linear motifs (SLiMs) within its short cytosolic C terminus. The proximal SLiM, by mimicking just a small portion of an R-N-ethylmaleimide-sensitive factor adaptor protein receptor (SNARE) motif, binds and recruits syntaxin (STX)7- and STX12-containing vesicles to the inclusion. The distal SLiM mimics the sorting nexin (SNX)5 and SNX6 cargo binding site to recruit SNX6-containing vesicles to the inclusion. By simultaneously binding two distinct vesicle classes, IncE brings these vesicles in close apposition with each other at the inclusion to facilitate C. trachomatis intracellular development. Our work suggests that Incs may have evolved SLiMs to enable rapid evolution in a limited protein space to disrupt host cell processes.
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  • 文章类型: Case Reports
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  • 文章类型: Journal Article
    自噬是真核细胞中普遍存在的降解体系。在植物中,尽管自噬体的生物发生已被广泛研究,自噬体如何转运到液泡进行降解的机制仍未被研究。在这项研究中,我们证明了自噬诱导后,拟南芥同型融合和蛋白质分选(HOPS)亚基VPS41首先从缩合物转化为斑点,然后是环状结构,称为VPS41相关的幻影空泡(VAPV),其中包含自噬相关基因(ATG)8s用于液泡降解。此过程由ADP核糖基化因子(ARF)样GTP酶ARLA1s启动,并通过与突触可溶性N-乙基马来酰亚胺敏感因子附着蛋白rmleceptor(SNARE)蛋白偶联与自噬进程同时发生。与其他真核生物不同,拟南芥的自噬降解在很大程度上独立于RAB7途径。相比之下,缩合物至VAPV转换过程中的功能障碍损害自噬体结构并破坏其液泡运输,导致自噬通量和植物存活率显着降低。我们的发现表明,转化途径可能是植物特有的自噬程序的组成部分。
    Autophagy is a universal degradation system in eukaryotic cells. In plants, although autophagosome biogenesis has been extensively studied, the mechanism of how autophagosomes are transported to the vacuole for degradation remains largely unexplored. In this study, we demonstrated that upon autophagy induction, Arabidopsis homotypic fusion and protein sorting (HOPS) subunit VPS41 converts first from condensates to puncta, then to ring-like structures, termed VPS41-associated phagic vacuoles (VAPVs), which enclose autophagy-related gene (ATG)8s for vacuolar degradation. This process is initiated by ADP ribosylation factor (ARF)-like GTPases ARLA1s and occurs concurrently with autophagy progression through coupling with the synaptic-soluble N-ethylmaleimide-sensitive factor attachment protein rmleceptor (SNARE) proteins. Unlike in other eukaryotes, autophagy degradation in Arabidopsis is largely independent of the RAB7 pathway. By contrast, dysfunction in the condensates-to-VAPVs conversion process impairs autophagosome structure and disrupts their vacuolar transport, leading to a significant reduction in autophagic flux and plant survival rate. Our findings suggest that the conversion pathway might be an integral part of the autophagy program unique to plants.
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  • 文章类型: Journal Article
    多年来,关于神经系统疾病发病机制的研究在世界范围内进展缓慢。然而,随着发病率的不断增加和疾病的逐渐发展,早期诊断和治疗已成为当务之急。SANP25,一种存在于突触前膜上并参与神经递质释放的蛋白质,与突触和神经元的丧失或异常表达亲密相干。SNAP25缺乏可导致突触障碍并抑制神经递质释放。因此,大量文献认为SNAP25基因突变是许多神经系统疾病的危险因素。这篇评论使用PubMed上的高级搜索对相关文献进行了广泛的文章搜索。搜索关键词包括SNAP25和阿尔茨海默病,SNAP25和帕金森病,等等。在阅读和总结以前的论文后,得出了相应的结论,达到了综述的目的。SNAP25的缺乏或变异可能与精神分裂症的发病有关。癫痫,注意力缺陷/活动障碍,双相情感障碍有效障碍,和自闭症。SNAP25已被发现用作神经疾病的神经病理学标志物,这可能是诊断或治疗阿尔茨海默病和帕金森病的目标。已经发现脑脊液(CSF)或血液能够实现更有效的药物开发。
    Over the years, research on the pathogenesis of neurological diseases has progressed slowly worldwide. However, as the incidence rate continues to increase and the disease gradually develops, early diagnosis and treatment have become a top priority. SANP25, a protein present on the presynaptic membrane and involved in neurotransmitter release, is closely related to the loss or abnormal expression of synapses and neurons. SNAP25 deficiency can lead to synaptic disorders and inhibit neurotransmitter release. Therefore, a large amount of literature believes that SNAP25 gene mutation is a risk factor for many neurological diseases. This review used advanced search on PubMed to conduct extensive article searches for relevant literature. The search keywords included SNAP25 and Alzheimer\'s disease, SNAP25 and Parkinson\'s disease, and so on. After reading and summarizing the previous papers, the corresponding conclusions were obtained to achieve the purpose of the review. The deficiency or variation of SNAP25 might be related to the onset of schizophrenia, epilepsy, attention deficit/hypoactivity disorder, bipolar disorder effective disorder, and autism. SNAP25 has been found to be used as a neuropathological marker for neurological diseases, which could be the target of diagnosis or treatment of Alzheimer\'s disease and Parkinson\'s disease. Cerebrospinal Fluid (CSF) or blood has been found to enable more effective drug development.
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  • 文章类型: Journal Article
    目的:探讨圈套器辅助牵引内镜下全层切除术(EFTR)治疗胃底黏膜下肿瘤(SMTs)的可行性和有效性。方法:收集2018年1月至2023年6月开封市中心医院内镜中心行EFTR治疗的胃部SMTs患者的临床病理资料。其中,36例患者接受了圈套器辅助牵引EFTR(SAT-EFTR),46例患者接受了标准EFTR(S-EFTR)。临床基线数据,手术数据,不良事件,收集并比较两组的随访结果。结果:所有患者均顺利完成EFTR技术。有34名男性和48名女性患者,平均年龄(56.62±11.31)岁。圈套器辅助EFTR组的平均手术时间短于S-EFTR组(73.39±31.33分钟比92.89±37.57分钟,P=.014)。此外,圈套器辅助EFTR组的切除速度也明显快于S-EFTR组(4.04±2.23比2.48±0.93mm2/min,P<.001)。年龄差异无统计学意义,性别,病变大小,术后禁食时间,两组患者术后住院时间及差异无统计学意义(P>.05)。SAT-EFTR组中的一名患者发生了延迟的术后穿孔,该穿孔与荷包缝合技术接近。所有患者均顺利出院,随访期间无复发或转移。结论:Snare辅助EFTR牵引可缩短手术时间,降低操作难度,提高运营效率。同时,此方法简单易学,更适合初学者,值得临床推广应用。
    Aim: To explore the feasibility and effectiveness of snare-assisted traction endoscopic full thickness resection (EFTR) on gastric fundus submucosal tumors (SMTs). Methods: The clinical and pathological data of patients with gastric SMTs who underwent EFTR treatment at the Endoscopy Center of Kaifeng Central Hospital from January 2018 to June 2023 were collected. Among them, 36 patients underwent snare-assisted traction EFTR (SAT-EFTR) and 46 patients underwent standard EFTR (S-EFTR). The clinical baseline data, operative data, adverse events, and follow-up results of the two groups were collected and compared. Results: All patients successfully completed EFTR technique. There were 34 male and 48 female patients, with an average age of (56.62 ± 11.31) years. The average operation time was shorter in the snare-assisted EFTR group than the S-EFTR group (73.39 ± 31.33 minutes versus 92.89 ± 37.57 minutes, P = .014). In addition, the resection speed of the snare-assisted EFTR group was also significantly faster than that of the S-EFTR group (4.04 ± 2.23 versus 2.48 ± 0.93 mm2/min, P < .001). There was no statistically significant difference in the age, gender, lesion size, postoperative fasting duration, and postoperative hospitalization stay between the two groups (P > .05). One patient in the SAT-EFTR group developed delayed postoperative perforation which was close with purse‑string suture technique. All patients were discharged successfully, and there was no recurrence or metastasis during the follow-up period. Conclusion: Snare-assisted traction of EFTR could shorten the operation time, reduce the difficulty of the operation, and improve the efficiency of the operation. At the same time, this method is simple and easy to learn, more suitable for beginners, and worthy of clinical promotion and application.
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  • 文章类型: Journal Article
    植物细胞中的细胞分裂始于将细胞壁材料运输到细胞分裂平面中心的囊泡融合,其中细胞板形成并径向膨胀,直到与亲本细胞壁融合。囊泡融合由反式-SNARE复合物促进,在Sec1/Munc18(SM)蛋白的帮助下。细胞板膜融合需要SNARE蛋白KNOLLE和SM蛋白KEULE。由于KEULE的关键功能,迄今为止鉴定的所有拟南芥(拟南芥)keule突变体都是幼苗致死性的。这里,我们鉴定了拟南芥serrata4-1(sea4-1)和sea4-2突变体,带有隐性,KEULE的低态等位基因。纯合的sea4-1和sea4-2植物是可行且可育的,但与野生型相比,玫瑰花结更小,抽苔时的叶子更少。它们的叶子是锯齿状的,小,波浪形,具有复杂的脉络模式。突变叶也发展坏死斑块并经历过早衰老。RNA-seq显示转录组变化可能导致细胞壁完整性降低和未折叠蛋白质反应增加。这些发现揭示了KEULE在胚胎后发育中的作用,特别是在莲座叶和叶缘的图案中。
    Cytokinesis in plant cells begins with the fusion of vesicles that transport cell wall materials to the center of the cell division plane, where the cell plate forms and expands radially until it fuses with the parental cell wall. Vesicle fusion is facilitated by trans-SNARE complexes, with assistance from Sec1/Munc18 (SM) proteins. The SNARE protein KNOLLE and the SM protein KEULE are required for membrane fusion at the cell plate. Due to the crucial function of KEULE, all Arabidopsis (Arabidopsis thaliana) keule mutants identified to date are seedling lethal. Here, we identified the Arabidopsis serrata4-1 (sea4-1) and sea4-2 mutants, which carry recessive, hypomorphic alleles of KEULE. Homozygous sea4-1 and sea4-2 plants are viable and fertile but have smaller rosettes and fewer leaves at bolting than the wild type. Their leaves are serrated, small, and wavy, with a complex venation pattern. The mutant leaves also develop necrotic patches and undergo premature senescence. RNA-seq revealed transcriptome changes likely leading to reduced cell wall integrity and an increase in the unfolded protein response. These findings shed light on the roles of KEULE in postembryonic development, particularly in the patterning of rosette leaves and leaf margins.
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  • 文章类型: Journal Article
    Syntaxin5(Syx5)属于SNAREs家族,在囊泡与靶膜的融合中起重要作用。我们对Syx5功能的了解大部分来自真菌或脊椎动物细胞的研究,Syx5在昆虫发育过程中的运作方式知之甚少。在这项研究中,我们研究了LmSyx5在半代谢昆虫蝗虫肠道发育中的作用。LmSyx5在许多组织中表达,肠道中的含量较高。通过RNA干扰(RNAi)敲除LmSyx5极大地抑制了若虫和成虫的摄食。注射dsLmSyx5的蝗虫体重减轻,最终以100%的死亡率死亡。此外,苏木精-伊红染色表明dsLmSyx5处理的若虫中肠变形,中肠上皮细胞刷状边界严重受损,表明LmSyx5参与中肠的形态发生。TEM进一步显示中肠细胞的内质网具有臃肿的外观。一起来看,这些结果表明,LmSyx5对影响迁徙乳杆菌生长和发育的中肠上皮稳态至关重要。因此,Syx5是一个有前途的RNAi靶标,用于控制迁徙乳杆菌,甚至其他害虫。
    Syntaxin5 (Syx5) belongs to SNAREs family, which play important roles in fusion of vesicles to target membranes. Most of what we know about functions of Syx5 originates from studies in fungal or vertebrate cells, how Syx5 operates during the development of insects is poorly understood. In this study, we investigated the role of LmSyx5 in the gut development of the hemimetabolous insect Locusta migratoria. LmSyx5 was expressed in many tissues, with higher levels in the gut. Knockdown of LmSyx5 by RNA interference (RNAi) considerably suppressed feeding in both nymphs and adults. The dsLmSyx5-injected locusts lost body weight and finally died at a mortality of 100%. Furthermore, hematoxylin-eosin staining indicated that the midgut is deformed in dsLmSyx5-treated nymphs and the brush border in midgut epithelial cells is severely damaged, suggesting that LmSyx5 is involved in morphogenesis of the midgut. TEM further showed that the endoplasmic reticulum of midgut cells have a bloated appearance. Taken together, these results suggest that LmSyx5 is essential for midgut epithelial homeostsis that affects growth and development of L. migratoria. Thus, Syx5 is a promising RNAi target for controlling L. migratoria, and even other pests.
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  • 文章类型: Case Reports
    我们报告了一例极为罕见的病例,该病例是在老年男性中进行经桡动脉冠状动脉造影以治疗不稳定型心绞痛的情况下,鹅颈圈套器辅助从主动脉弓取回栓塞的冠状动脉导丝。在这种情况下,使用花瓣圈套器无法从肱动脉或主动脉根部取回栓塞的冠状动脉导丝的近端。从这种情况下的关键结论是,可以在诸如主动脉弓之类的中等宽敞区域中,用鹅颈圈套器从近端成功取回栓塞的冠状动脉导丝。
    We report an extremely rare case of gooseneck snare-assisted retrieval of an embolized coronary guidewire from the aortic arch in an elderly male scheduled for a transradial coronary angiogram for unstable angina. In this case, the proximal end of the embolized coronary guidewire could not be retrieved from the brachial artery nor the roomy aortic root using a flower petal snare. The key takeaway from this case is that an embolized coronary guidewire can be successfully retrieved with a gooseneck snare from its proximal end in a moderately spacious area like the aortic arch.
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  • 文章类型: Journal Article
    在巨自噬期间,细胞质成分被自噬体吞噬。溶酶体与封闭的自噬体融合,但不与未封闭的中间结构融合。这在一定程度上是通过将自噬体SNARE突触蛋白17(STX17)晚期募集到成熟的自噬体来实现的。然而,STX17如何识别自噬体成熟尚不清楚。这里,我们表明,STX17的这种时间调节的募集取决于STX17的带正电荷的C末端区域。与这一发现一致,成熟的自噬体与未封闭的中间结构相比带负电。自噬体的静电成熟可能是由自噬体膜中磷脂酰肌醇4-磷酸(PI4P)的积累驱动的。因此,自噬体PI4P的去磷酸化阻止了STX17与自噬体的关联。此外,分子动力学模拟支持STX17跨膜螺旋的PI4P依赖性膜插入。基于这些发现,我们提出了一个模型,在该模型中,成熟自噬体的STX17募集受到PI4P驱动的自噬体表面电荷变化的时间调控.
    During macroautophagy, cytoplasmic constituents are engulfed by autophagosomes. Lysosomes fuse with closed autophagosomes but not with unclosed intermediate structures. This is achieved in part by the late recruitment of the autophagosomal SNARE syntaxin 17 (STX17) to mature autophagosomes. However, how STX17 recognizes autophagosome maturation is not known. Here, we show that this temporally regulated recruitment of STX17 depends on the positively charged C-terminal region of STX17. Consistent with this finding, mature autophagosomes are more negatively charged compared with unclosed intermediate structures. This electrostatic maturation of autophagosomes is likely driven by the accumulation of phosphatidylinositol 4-phosphate (PI4P) in the autophagosomal membrane. Accordingly, dephosphorylation of autophagosomal PI4P prevents the association of STX17 to autophagosomes. Furthermore, molecular dynamics simulations support PI4P-dependent membrane insertion of the transmembrane helices of STX17. Based on these findings, we propose a model in which STX17 recruitment to mature autophagosomes is temporally regulated by a PI4P-driven change in the surface charge of autophagosomes.
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  • 文章类型: Journal Article
    自噬体膜电荷的变化控制SNARE蛋白的募集,以确保膜融合在自噬过程中的正确时间发生。
    A change in the electric charge of autophagosome membranes controls the recruitment of SNARE proteins to ensure that membrane fusion occurs at the right time during autophagy.
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