• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

Rabs、SNAREs和MAL在尿路上皮伞细胞梭形囊泡顶端递送中的顺序性和区室化作用。

Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells.

作者信息

Wankel Bret, Ouyang Jiangyong, Guo Xuemei, Hadjiolova Krassimira, Miller Jeremy, Liao Yi, Tham Daniel Kai Long, Romih Rok, Andrade Leonardo R, Gumper Iwona, Simon Jean-Pierre, Sachdeva Rakhee, Tolmachova Tanya, Seabra Miguel C, Fukuda Mitsunori, Schaeren-Wiemers Nicole, Hong Wan Jin, Sabatini David D, Wu Xue-Ru, Kong Xiangpeng, Kreibich Gert, Rindler Michael J, Sun Tung-Tien

机构信息

Department of Cell Biology, New York University School of Medicine, New York, NY10016.

Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.

出版信息

Mol Biol Cell. 2016 May 15;27(10):1621-34. doi: 10.1091/mbc.E15-04-0230. Epub 2016 Mar 23.

DOI:10.1091/mbc.E15-04-0230
PMID:27009205
原文链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC4865319/
Abstract

Uroplakins (UPs) are major differentiation products of urothelial umbrella cells and play important roles in forming the permeability barrier and in the expansion/stabilization of the apical membrane. Further, UPIa serves as a uropathogenic Escherichia coli receptor. Although it is understood that UPs are delivered to the apical membrane via fusiform vesicles (FVs), the mechanisms that regulate this exocytic pathway remain poorly understood. Immunomicroscopy of normal and mutant mouse urothelia show that the UP-delivering FVs contained Rab8/11 and Rab27b/Slac2-a, which mediate apical transport along actin filaments. Subsequently a Rab27b/Slp2-a complex mediated FV-membrane anchorage before SNARE-mediated and MAL-facilitated apical fusion. We also show that keratin 20 (K20), which forms a chicken-wire network ∼200 nm below the apical membrane and has hole sizes allowing FV passage, defines a subapical compartment containing FVs primed and strategically located for fusion. Finally, we show that Rab8/11 and Rab27b function in the same pathway, Rab27b knockout leads to uroplakin and Slp2-a destabilization, and Rab27b works upstream from MAL. These data support a unifying model in which UP cargoes are targeted for apical insertion via sequential interactions with Rabs and their effectors, SNAREs and MAL, and in which K20 plays a key role in regulating vesicular trafficking.

摘要

尿血小板溶素（UPs）是尿路上皮伞细胞的主要分化产物，在形成渗透屏障以及顶端膜的扩张/稳定过程中发挥重要作用。此外，UPIa可作为尿路致病性大肠杆菌的受体。尽管已知UPs通过梭形囊泡（FV）被递送至顶端膜，但调节这种胞吐途径的机制仍知之甚少。对正常和突变小鼠尿路上皮的免疫显微镜检查显示，递送UP的FV含有Rab8/11和Rab27b/Slac2-a，它们沿肌动蛋白丝介导顶端运输。随后，Rab27b/Slp2-a复合物在SNARE介导和MAL促进的顶端融合之前介导FV与膜的锚定。我们还表明，角蛋白20（K20）在顶端膜下方约200 nm处形成一个铁丝网样网络，其孔大小允许FV通过，它定义了一个包含经预处理且处于战略融合位置的FV的亚顶端区室。最后，我们表明Rab8/11和Rab27b在同一途径中发挥作用，Rab27b基因敲除导致尿血小板溶素和Slp2-a不稳定，并且Rab27b在MAL的上游起作用。这些数据支持了一个统一模型，即UP货物通过与Rabs及其效应器、SNAREs和MAL的顺序相互作用而靶向顶端插入，并且K20在调节囊泡运输中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/54d62f8aa641/1621fig14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/2abd220901a7/1621fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/240a6a2cc89b/1621fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/cb17594b1289/1621fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/17159a2389b9/1621fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/ae6a4d02ffa4/1621fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/e8c774da900d/1621fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/1f86552884ea/1621fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/6ef7c964a05e/1621fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/2af3bdaac689/1621fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/7ffddcc57ccc/1621fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/4d71e5e98c43/1621fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/53d269491717/1621fig12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/7c23c145ae28/1621fig13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/54d62f8aa641/1621fig14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/2abd220901a7/1621fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/240a6a2cc89b/1621fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/cb17594b1289/1621fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/17159a2389b9/1621fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/ae6a4d02ffa4/1621fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/e8c774da900d/1621fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/1f86552884ea/1621fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/6ef7c964a05e/1621fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/2af3bdaac689/1621fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/7ffddcc57ccc/1621fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/4d71e5e98c43/1621fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/53d269491717/1621fig12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/7c23c145ae28/1621fig13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/011a/4865319/54d62f8aa641/1621fig14.jpg

相似文献

1
Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells.Rabs、SNAREs和MAL在尿路上皮伞细胞梭形囊泡顶端递送中的顺序性和区室化作用。
Mol Biol Cell. 2016 May 15;27(10):1621-34. doi: 10.1091/mbc.E15-04-0230. Epub 2016 Mar 23.
2
MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells.MAL 促进了分泌性尿路上皮素囊泡纳入尿路上皮伞细胞顶膜的过程。
Mol Biol Cell. 2012 Apr;23(7):1354-66. doi: 10.1091/mbc.E11-09-0823. Epub 2012 Feb 9.
3
Rab27b is associated with fusiform vesicles and may be involved in targeting uroplakins to urothelial apical membranes.Rab27b与梭形囊泡相关，可能参与将尿路上皮蛋白靶向输送到尿路上皮顶端膜。
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14012-7. doi: 10.1073/pnas.2436350100. Epub 2003 Nov 18.
4
Involvement of vps33a in the fusion of uroplakin-degrading multivesicular bodies with lysosomes.vps33a 在 uroplakin 降解多泡体与溶酶体融合中的作用。
Traffic. 2009 Sep;10(9):1350-61. doi: 10.1111/j.1600-0854.2009.00950.x. Epub 2009 May 26.
5
SNX31: a novel sorting nexin associated with the uroplakin-degrading multivesicular bodies in terminally differentiated urothelial cells.分选连接蛋白31：一种与终末分化的尿路上皮细胞中降解尿膜蛋白的多囊泡体相关的新型分选连接蛋白
PLoS One. 2014 Jun 10;9(6):e99644. doi: 10.1371/journal.pone.0099644. eCollection 2014.
6
A non-canonical autophagy-dependent role of the ATG16L1 variant in urothelial vesicular trafficking and uropathogenic Escherichia coli persistence.ATG16L1 变异体在非经典自噬依赖性中的作用：对尿路上皮囊泡运输和尿路致病性大肠杆菌持续存在的影响。
Autophagy. 2019 Mar;15(3):527-542. doi: 10.1080/15548627.2018.1535290. Epub 2018 Nov 8.
7
What determines differentiation of urothelial umbrella cells?是什么决定了尿路上皮伞细胞的分化？
Eur J Cell Biol. 2004 Feb;83(1):27-34. doi: 10.1078/0171-9335-00351.
8
Golgi apparatus fragmentation as a mechanism responsible for uniform delivery of uroplakins to the apical plasma membrane of uroepithelial cells.高尔基器碎片化作为一种机制负责将尿路上皮细胞顶质膜均匀地递送到尿路上皮细胞的顶质膜。
Biol Cell. 2010 Nov;102(11):593-607. doi: 10.1042/BC20100024.
9
Expression and localization of four uroplakins in urothelial preneoplastic lesions.四种尿路上皮癌前病变中尿路上皮蛋白的表达和定位。
Histochem Cell Biol. 2011 Oct;136(4):491-500. doi: 10.1007/s00418-011-0857-4. Epub 2011 Aug 19.
10
RAB27B requirement for stretch-induced exocytosis in bladder umbrella cells.RAB27B 对膀胱伞细胞牵张诱导胞吐作用的需求。
Am J Physiol Cell Physiol. 2018 Mar 1;314(3):C349-C365. doi: 10.1152/ajpcell.00218.2017. Epub 2017 Nov 22.

引用本文的文献

1
Ultrasound-assisted intravesical botulinum toxin A delivery attenuates acetic acid-induced bladder hyperactivity in rats.超声辅助膀胱内注射A型肉毒杆菌毒素可减轻醋酸诱导的大鼠膀胱功能亢进。
Front Pharmacol. 2023 Jul 24;14:1214145. doi: 10.3389/fphar.2023.1214145. eCollection 2023.
2
α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification.α-溶血素通过破坏细菌藏匿的溶酶体酸化促进泌尿道致病性大肠杆菌在膀胱上皮细胞中的持续存在。
PLoS Pathog. 2023 May 11;19(5):e1011388. doi: 10.1371/journal.ppat.1011388. eCollection 2023 May.
3
The urothelium: a multi-faceted barrier against a harsh environment.

本文引用的文献

1
Dual ligand/receptor interactions activate urothelial defenses against uropathogenic E. coli.双配体/受体相互作用激活尿路上皮对尿路致病性大肠杆菌的防御。
Sci Rep. 2015 Nov 9;5:16234. doi: 10.1038/srep16234.
2
Evidence for changes in beta- and gamma-actin proportions during inner ear hair cell life.内耳毛细胞生命周期中β-肌动蛋白和γ-肌动蛋白比例变化的证据。
Cytoskeleton (Hoboken). 2015 Jun;72(6):282-91. doi: 10.1002/cm.21227. Epub 2015 Jun 30.
3
Vesicle associated membrane protein 8 (VAMP8)-mediated zymogen granule exocytosis is dependent on endosomal trafficking via the constitutive-like secretory pathway.
尿路上皮：恶劣环境下的多面屏障。
Mucosal Immunol. 2022 Jun;15(6):1127-1142. doi: 10.1038/s41385-022-00565-0. Epub 2022 Sep 30.
4
Myosin 5a in the Urinary Bladder: Localization, Splice Variant Expression, and Functional Role in Neurotransmission.膀胱中的肌球蛋白5a：定位、剪接变体表达及其在神经传递中的功能作用
Front Physiol. 2022 Jul 1;13:890102. doi: 10.3389/fphys.2022.890102. eCollection 2022.
5
Tip-end fusion of a rod-shaped secretory organelle.棒状分泌细胞器的尖端融合。
Cell Mol Life Sci. 2022 Jun 4;79(6):344. doi: 10.1007/s00018-022-04367-2.
6
Current methods to analyze lysosome morphology, positioning, motility and function.目前分析溶酶体形态、定位、运动和功能的方法。
Traffic. 2022 May;23(5):238-269. doi: 10.1111/tra.12839. Epub 2022 Apr 24.
7
CNS endothelial derived extracellular vesicles are biomarkers of active disease in multiple sclerosis.中枢神经系统内皮细胞衍生的细胞外囊泡是多发性硬化症活动期的生物标志物。
Fluids Barriers CNS. 2022 Feb 8;19(1):13. doi: 10.1186/s12987-021-00299-4.
8
BoNT/A in the Urinary Bladder-More to the Story than Silencing of Cholinergic Nerves.肉毒毒素 A 作用于膀胱——不仅仅是抑制胆碱能神经。
Toxins (Basel). 2022 Jan 12;14(1):53. doi: 10.3390/toxins14010053.
9
In vivo Roles of Rab27 and Its Effectors in Exocytosis.Rab27 及其效应物在胞吐作用中的体内作用。
Cell Struct Funct. 2021 Nov 6;46(2):79-94. doi: 10.1247/csf.21043. Epub 2021 Sep 4.
10
The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer.MAL 蛋白，一种特殊膜的基本组成部分，存在于正常细胞和癌细胞中。
Cells. 2021 Apr 30;10(5):1065. doi: 10.3390/cells10051065.
囊泡相关膜蛋白8（VAMP8）介导的酶原颗粒胞吐作用依赖于通过组成型分泌途径的内体运输。
J Biol Chem. 2014 Oct 3;289(40):28040-53. doi: 10.1074/jbc.M114.593913. Epub 2014 Aug 19.
4
SNX31: a novel sorting nexin associated with the uroplakin-degrading multivesicular bodies in terminally differentiated urothelial cells.分选连接蛋白31：一种与终末分化的尿路上皮细胞中降解尿膜蛋白的多囊泡体相关的新型分选连接蛋白
PLoS One. 2014 Jun 10;9(6):e99644. doi: 10.1371/journal.pone.0099644. eCollection 2014.
5
Distinct actions of Rab3 and Rab27 GTPases on late stages of exocytosis of insulin.Rab3和Rab27 GTP酶对胰岛素胞吐作用后期的不同作用。
Traffic. 2014 Sep;15(9):997-1015. doi: 10.1111/tra.12182. Epub 2014 Jun 26.
6
Myosin Va mediates Rab8A-regulated GLUT4 vesicle exocytosis in insulin-stimulated muscle cells.肌球蛋白Va介导胰岛素刺激的肌肉细胞中Rab8A调节的葡萄糖转运蛋白4囊泡胞吐作用。
Mol Biol Cell. 2014 Apr;25(7):1159-70. doi: 10.1091/mbc.E13-08-0493. Epub 2014 Jan 29.
7
Rab27 effectors, pleiotropic regulators in secretory pathways.Rab27 效应物：分泌途径中的多效调节因子。
Traffic. 2013 Sep;14(9):949-63. doi: 10.1111/tra.12083. Epub 2013 Jun 10.
8
A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells.Rab11a-Rab8a-Myo5B 网络促进膀胱伞细胞的拉伸调节型胞吐作用。
Mol Biol Cell. 2013 Apr;24(7):1007-19. doi: 10.1091/mbc.E12-08-0568. Epub 2013 Feb 6.
9
Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells.突触融合蛋白样蛋白控制上皮细胞中单一顶端膜结构域的形成。
Nat Cell Biol. 2012 Aug;14(8):838-49. doi: 10.1038/ncb2541. Epub 2012 Jul 22.
10
Syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet secretion.Syntaxin-11 而非 syntaxin-2 或 syntaxin-4 对于血小板分泌是必需的。
Blood. 2012 Sep 20;120(12):2484-92. doi: 10.1182/blood-2012-05-430603. Epub 2012 Jul 5.