更新于：2024-11-01

SNAP29

更新于：2024-11-01

基本信息

别名

CEDNIK、SNAP-29、SNAP29

+ [4]

简介

SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Also plays a role in ciliogenesis by regulating membrane fusions.

关联

100 项与 SNAP29 相关的临床结果

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100 项与 SNAP29 相关的转化医学

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0 项与 SNAP29 相关的专利（医药）

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240

项与 SNAP29 相关的文献（医药）

2024-11-04·The Journal of cell biology

Migfilin promotes autophagic flux through direct interaction with SNAP29 and Vamp8.

Article

作者: Ding, Yanyan ; Bai, Panzhu ; Zhao, Yan G ; Liu, Chengmin ; Wu, Chuanyue ; Xiong, Zailin ; Cai, Renwei ; Tian, Ruijun ; Wei, Wenjie ; Li, Binbin ; Deng, Yi ; Sun, Ying ; Yang, Aihua ; Quan, Meiling ; Li, Guizhen

Autophagy plays a crucial role in cancer cell survival by facilitating the elimination of detrimental cellular components and the recycling of nutrients. Understanding the molecular regulation of autophagy is critical for developing interventional approaches for cancer therapy. In this study, we report that migfilin, a focal adhesion protein, plays a novel role in promoting autophagy by increasing autophagosome-lysosome fusion. We found that migfilin is associated with SNAP29 and Vamp8, thereby facilitating Stx17-SNAP29-Vamp8 SNARE complex assembly. Depletion of migfilin disrupted the formation of the SNAP29-mediated SNARE complex, which consequently blocked the autophagosome-lysosome fusion, ultimately suppressing cancer cell growth. Restoration of the SNARE complex formation rescued migfilin-deficiency-induced autophagic flux defects. Finally, we found depletion of migfilin inhibited cancer cell proliferation. SNARE complex reassembly successfully reversed migfilin-deficiency-induced inhibition of cancer cell growth. Taken together, our study uncovers a new function of migfilin as an autophagy-regulatory protein and suggests that targeting the migfilin-SNARE assembly could provide a promising therapeutic approach to alleviate cancer progression.

2024-11-01·Microbial Pathogenesis

Comprehensive analysis of the mRNA and miRNA transcriptome implicated in the immune response of Procambarus clarkii to Spiroplasma eriocheiris

Article

作者: Chen, Hao ; Dong, Huizi ; Liu, Yang ; Wang, Xiang ; Zhao, Weihong ; Zhang, Benhou ; Xu, Zheqi ; Yu, Shuai ; Ou, Jiangtao ; Luan, Xiaoqi

In recent years, the red swamp crayfish (Procambarus clarkii, P. clarkii) farming industry has suffered huge economic losses due to the pathogenic bacterium Spiroplasma eriocheiris (S. eriocheiris). To elucidate the immune response mechanism and identify hub immune genes as well as their associated microRNAs that regulate the host response of P. clarkii against S. eriocheiris infection, we conducted a comprehensive analysis on P. clarkii hemocyte mRNA and microRNA (miRNA) transcriptomes at different infection stages using third- and second-generation sequencing technologies. In full-length transcriptome functional annotation, 8155 unigenes were annotated, and 1168 potential new transcripts were predicted. In the mRNA transcriptome, a total of 3168 differentially expressed genes were identified at different infection stages, including 1492 upregulated and 1676 downregulated genes (duplicate genes excluded). Transcriptome analysis revealed 880 differentially expressed genes involved in multiple pathways and processes such as endocytosis, autophagy, lysosome, mTOR signaling, phagosome, and the Fanconi anemia pathway. Mfuzz analysis was employed to integrate and cluster the differential expression trends of genes across the three infection stages. In the miRNA transcriptome, 234 miRNAs and 966 predicted target genes were identified, with 86 differentially expressed miRNAs identified across the three time periods. A significant difference (P < 0.05) was observed for miRNAs including pcl-miR-146-3p, pcl-miR-74-3p, pcl-miR-225-5p, and pcl-miR-68-5p. These miRNAs are involved in multiple immune and autophagy-related pathways and have regulatory effects on immune genes including Vps26, lqf, and ERK-A. Based on the differentially expressed immune-related genes, we constructed a protein-protein interaction (PPI) network, which revealed the interactions among hub genes including Rac1, Akt1, Rho1, and Egfr. We also constructed a miRNA-gene interaction network in immune and autophagy-related processes, highlighting the potential regulatory effects of miRNAs including pcl-miR-183-5p, pcl-miR-146-3p, pcl-miR-176-5p, and pcl-miR-225-5p on proteins including LST8, SNAP29, Rab-7A, and ERK-A. To conclude, this study has identified hub immune genes and corresponding regulatory miRNAs in P. clarkii hemocytes in response to S. eriocheiris infection and explored the roles of these genes in selected pathways and processes. These findings are expected to provide further insights into the molecular mechanisms that confer resistance to S. eriocheiris infection in P. clarkii.

2024-10-02·Autophagy

Secretory autophagy – a new paradigm regulating synaptic plasticity

Article

作者: Chang, Yen-Ching ; Chang, Karen T.

When exposed to new experiences or changes in the environment, neurons rapidly remodel their synaptic structure and function in a process called activity-induced synaptic remodeling. This process is necessary for transforming transient experiences into stable, lasting memories. The molecular mechanisms underlying acute, activity-dependent synaptic changes are not well understood, partly because processes regulating synaptic plasticity and neurodevelopment are intricately linked. By using an RNAi screen in Drosophila targeting genes associated with human nervous system function, we found that while macroautophagy (referred to as autophagy) is fundamental for both synapse development and synaptic plasticity, activity-induced synaptic remodeling does not rely on genes associated with lysosomal degradation. These findings suggest a requirement for the unconventional secretory autophagy pathway in regulating synaptic plasticity, wherein autophagosomes, instead of fusing with lysosomes for degradation, fuse with the plasma membrane to release their contents extracellularly. To test this hypothesis, we knocked down Sec22, Snap29, and Rab8, molecular components required for secretory autophagy, all of which disrupted structural and functional plasticity. Additionally, by monitoring autophagy, we demonstrated that neuronal activity suppresses degradative autophagy to shift the pathway toward secretory autophagy release. Our work unveils secretory autophagy as a novel trans-synaptic signaling mechanism crucial for activity-induced synaptic remodeling.

项与 SNAP29 相关的新闻（医药）

2024-10-13

·生物探索

Cell | TEX264驱动的选择性自噬促进DNA修复和细胞存活

引言 DNA 修复和自噬是维持细胞生存的两个关键生物学过程。DNA修复负责修复DNA损伤，确保基因组稳定；而自噬则负责清除细胞内多余的、受损的、错误折叠或聚集的蛋白质和细胞器，维持细胞稳态。拓扑异构酶 I (TOP1) 在DNA复制和转录中起着至关重要的作用，它通过切断DNA形成超螺旋结构，释放扭转应力。然而，TOP1与DNA形成的共价键——TOP1cc是一种有害的DNA损伤，会导致基因组不稳定和细胞死亡。TOP1cc修复主要依赖于酪氨酸DNA磷酸二酯酶 1 (TDP1) 介导的切除修复或MRE11核酶介导的DNA切割和切除修复【1】。然而，TOP1cc的修复过程与蛋白质降解途径的关系尚不清楚。自噬因子在DNA复制叉附近富集，表明自噬可能在DNA损伤修复中发挥作用。TEX264是一种保守的蛋白质，既是自噬受体，也与TOP1cc修复有关【2】。然而，TEX264是否通过自噬介导TOP1cc修复，目前尚不清楚。近日，来自英国牛津大学拉德克利夫医院的Kristijan Ramadan研究团队在Cell杂志上发表题为TEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival的研究论文，该研究发现了TEX264介导的核吞噬作用在维持基因组稳定性和细胞存活中发挥关键作用。首先通过免疫共沉淀和蛋白质组学分析，研究人员发现自噬相关蛋白（如Beclin-1、TEX264、CHMP7、ATG7、SNAP29）在DNA复制叉处富集，并且这种富集在CPT（诱导DNA复制压力的化合物）处理后被显著增强，这表明自噬可能在响应 DNA 复制压力时发挥作用。接着，研究人员使用LysoIP技术分离溶酶体，并通过质谱分析其蛋白质组成。结果表明，CPT 处理后，许多DNA复制和核蛋白（如DNA聚合酶、MCM复合物蛋白、核孔复合物）被运送到溶酶体，表明溶酶体可能直接参与 DNA 损伤的清除。进一步，研究人员发现用CPT处理后，TOP1cc水平的恢复受到mTOR抑制剂Torin的促进，而自噬抑制剂ATG7的缺失则完全阻止了TOP1cc的修复，证明自噬是TOP1cc修复的关键途径。其他自噬相关蛋白，如syntaxin 17和RB1CC1，也参与了TOP1cc的降解和细胞对CPT的存活，说明自噬修复TOP1cc的过程是一个复杂的网络，涉及多个自噬相关蛋白。使用mCherry-TOP1-GFP报告系统证实了TOP1在低剂量CPT处理后进入溶酶体，表明 TOP1cc可以直接被溶酶体降解。通过分析γ-H2AX 和53BP1的定位，研究人员发现低剂量CPT诱导的DNA损伤主要表现为复制压力，而不是DNA 双链断裂。此外，研究人员发现ATR抑制剂VE-822强烈抑制了TOP1cc的运送，而ATM抑制剂KU-55933没有影响，这表明ATR在响应DNA复制压力和促进 TOP1cc 降解中起着关键作用。自噬抑制剂ATG7和syntaxin 17的缺失加剧了低剂量 CPT 处理后蛋白质聚集物的形成，说明自噬在防止蛋白质聚集物形成中发挥作用。最后，研究人员发现MRE11核酶的缺失强烈抑制了TOP1cc的运送，而MUS81和TDP1的缺失没有影响，表明MRE11核酶在将TOP1cc从核内运送到溶酶体中起着关键作用。使用 LysoIP-Seq技术分离溶酶体中的DNA片段，并通过测序分析其序列特征。结果表明，溶酶体中分离的DNA片段主要来自核内 DNA，且大部分来自内含子和着丝粒区域，表明溶酶体可以清除整个TOP1cc损伤，包括其蛋白质部分和相关的DNA片段。使用 TOP1cc 特异性抗体和LysoIP等技术证实了TOP1cc在低剂量CPT处理后在细胞质中的存在。这表明 TOP1cc可以从核内被运送到细胞质，并被溶酶体降解。图1 TEX264驱动的选择性自噬促进DNA修复和细胞存活（Credit: Cell）总之，这项研究证明了选择性自噬在DNA修复中的进化保守作用，并表明它对维持基因组稳定性和细胞存活至关重要。此外，该发现还表明，在治疗结直肠癌患者时， TEX264的表达水平与对伊立替康等TOP1抑制剂的化疗反应相关。参考文献 1. Pommier, Y. (2006). Topoisomerase I inhibitors: camptothecins and beyond. Nat. Rev. Cancer 6, 789–802. https://doi-org.libproxy1.nus.edu.sg/10.1038/nrc1977.7. Stingele, J., Bellelli, R., and Boulton, S.J. (2017). Mechanisms of DNA–protein crosslink repair. Nat. Rev. Mol. Cell Biol. 18, 563–573. 2. Fielden, J., Wiseman, K., Torrecilla, I., Li, S., Hume, S., Chiang, S.-C., Ruggiano, A., Narayan Singh, A., Freire, R., Hassanieh, S., et al. (2020). TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts. Nat. Commun. 11, 1274. https://www-cell-com.libproxy1.nus.edu.sg/cell/fulltext/S0092-8674(24)00911-5 责编|探索君排版|探索君文章来源|“BioArt” 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 Cell | 是什么决定了细胞的大小？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 CRISPR技术进化史 | 24年Cell综述

2023-06-20

·生物谷

科学家揭示了PPD是一种靶向CMA抑制剂，是非小细胞肺癌治疗的好策略

自噬是细胞中的一种“自噬”现象，自噬小体包裹错误折叠的蛋白质或受损的细胞器，随后与溶酶体融合形成自溶酶体。被包裹的内容物被自溶酶体降解，以实现细胞内环境的稳定和细胞器的更新。自噬是细胞中的一种“自噬”现象，自噬小体包裹错误折叠的蛋白质或受损的细胞器，随后与溶酶体融合形成自溶酶体。被包裹的内容物被自溶酶体降解，以实现细胞内环境的稳定和细胞器的更新。根据自噬的发生过程，自噬可分为巨型自噬、伴侣介导型自噬和微型自噬。其中，CMA是一种选择性的以Lys-Phe-Glu-Arg-Gln(KFERQ)样五肽基序为靶向的蛋白质降解自噬。KFERQ类基序要么存在于初级氨基酸序列中，要么通过翻译后修饰产生，如磷酸化或乙酰化。胞内伴侣热休克同源蛋白70(HSC70)可以识别含有KFERQ样基序的底物蛋白，随后底物-伴侣复合体通过与溶酶体膜蛋白2A型(LAMP2A)结合转移到溶酶体膜上，并驱动LAMP2A型多聚体形成易位复合体，底物通过该复合体进入溶酶体进行降解。图片来源：https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/37311689/ 近日，来自中国药科大学的研究者们在Br J Pharmacol杂志上发表了题为“Discovery of a potent inhibitor of chaperone-mediated autophagy that targets the HSC70-LAMP2A interaction in non-small cell lung cancer therapy”的文章，该研究揭示了PPD是一种靶向CMA抑制剂，可以阻断HSC70LAMP2A相互作用和LAMP2A同源多聚化。抑制CMA而不增加巨噬细胞自噬的调节补偿是非小细胞肺癌治疗的好策略。伴侣介导的自噬(CMA)是一种选择性的针对蛋白质降解的自噬，在多种恶性肿瘤中保持高活性。抑制HSC70和LAMP2A的结合可以有效地阻断CMA。目前，抑制CMA的最具特异性的方法仍然是下调LAMP2A，目前还没有发现抑制CMA的化学抑制剂。用酪胺信号放大(TSA)双免疫荧光法检测NSCLC组织中CMA的表达水平。根据CMA活性进行高含量筛选，以确定潜在的CMA抑制剂。通过药物亲和反应靶标稳定性-质谱法(DARTS-MS)确定了该抑制剂的靶点，并用蛋白质质谱仪进行了验证。通过对CMA的抑制和激活来阐明CMA抑制剂的分子机制。研究者发现，抑制HSC70和LAMP2A之间的相互作用可以阻断非小细胞肺癌中的CMA，并抑制肿瘤的生长。PPD通过干扰HSC70-LAMP2A相互作用首次被确定为CMA的靶向小分子抑制剂。 PPD的结合位点分别位于HSC70的核苷酸结合区E129和LAMP2A的C末端T278。PPD通过抑制HSC70-LAMP2a-eIF2α信号轴，加速蛋白质合成，诱导ROS积累。此外，PPD还通过阻断STX17-SNAP29-VAMP8信号轴，阻止了CMA抑制引起的巨噬细胞自噬的调节补偿。图片来源：https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/37311689/ PPD阻断非小细胞肺癌CMA的作用机制综上所述，研究者首次报道PPD是非小细胞肺癌中CMA的靶向抑制剂。更重要的是，本研究为开发CMA抑制剂提供了新的策略。靶向抑制HSC70-LAMP2A相互作用或LAMP2A同源多聚化对非小细胞肺癌的治疗具有很强的疗效。（生物谷 Bioon.com）参考文献 Rui-Fang Dong et al. Discovery of a potent inhibitor of chaperone-mediated autophagy that targets the HSC70-LAMP2A interaction in non-small cell lung cancer therapy. Br J Pharmacol. 2023 Jun 13. doi: 10.1111/bph.16165.