• 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

两种逆行微管马达分别驱动早期和晚期内涵体运输。

Distinct retrograde microtubule motor sets drive early and late endosome transport.

机构信息

Department of Oncology, University of Torino School of Medicine, Candiolo, Italy.

Candiolo Cancer Institute - Fondazione del Piemonte per l'Oncologia (FPO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Torino, Italy.

出版信息

EMBO J. 2020 Dec 15;39(24):e103661. doi: 10.15252/embj.2019103661. Epub 2020 Nov 20.

DOI:10.15252/embj.2019103661
PMID:33215754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7737607/
Abstract

Although subcellular positioning of endosomes significantly impacts on their functions, the molecular mechanisms governing the different steady-state distribution of early endosomes (EEs) and late endosomes (LEs)/lysosomes (LYs) in peripheral and perinuclear eukaryotic cell areas, respectively, are still unsolved. We unveil that such differences arise because, while LE retrograde transport depends on the dynein microtubule (MT) motor only, the one of EEs requires the cooperative antagonism of dynein and kinesin-14 KIFC1, a MT minus end-directed motor involved in cancer progression. Mechanistically, the Ser-x-Ile-Pro (SxIP) motif-mediated interaction of the endoplasmic reticulum transmembrane protein stromal interaction molecule 1 (STIM1) with the MT plus end-binding protein 1 (EB1) promotes its association with the p150Glued subunit of the dynein activator complex dynactin and the distinct location of EEs and LEs/LYs. The peripheral distribution of EEs requires their p150Glued-mediated simultaneous engagement with dynein and SxIP motif-containing KIFC1, via HOOK1 and HOOK3 adaptors, respectively. In sum, we provide evidence that distinct minus end-directed MT motor systems drive the differential transport and subcellular distribution of EEs and LEs in mammalian cells.

摘要

尽管内体的亚细胞定位对其功能有重要影响，但仍未解决早期内体（EEs）和晚期内体（LEs）/溶酶体（LYs）分别在细胞质和核周真核细胞区的稳定状态分布的分子机制。我们揭示了这种差异的产生，是因为 LE 的逆行运输仅依赖于动力蛋白微管（MT）马达，而 EE 的逆行运输则需要动力蛋白和驱动蛋白-14 KIFC1 的协同拮抗作用，KIFC1 是一种参与癌症进展的 MT 负端导向马达。从机制上讲，内质网跨膜蛋白基质相互作用分子 1（STIM1）与 MT 加端结合蛋白 1（EB1）之间的 Ser-x-Ile-Pro（SxIP）基序介导的相互作用促进了其与动力蛋白激活复合物 dynactin 的 p150Glued 亚基的结合，以及 EE 和 LE/LYs 的不同位置。EE 的外周分布需要其 p150Glued 通过 HOOK1 和 HOOK3 接头分别与动力蛋白和包含 SxIP 基序的 KIFC1 同时结合。总之，我们提供了证据，表明不同的 MT 负端导向马达系统驱动了哺乳动物细胞中 EE 和 LE 的差异运输和亚细胞分布。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/af994ac85ba6/EMBJ-39-e103661-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/2ce13b6f4586/EMBJ-39-e103661-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/7e45adc3d8f9/EMBJ-39-e103661-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/faa106320685/EMBJ-39-e103661-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/11faccf80064/EMBJ-39-e103661-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/f022e0e11a94/EMBJ-39-e103661-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/1da8248ca9e2/EMBJ-39-e103661-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/3dcd1cbf4764/EMBJ-39-e103661-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/215226cea139/EMBJ-39-e103661-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/0e2e694e2c4d/EMBJ-39-e103661-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/1fe9cd078ed2/EMBJ-39-e103661-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/ce733fe608b6/EMBJ-39-e103661-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/af994ac85ba6/EMBJ-39-e103661-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/2ce13b6f4586/EMBJ-39-e103661-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/7e45adc3d8f9/EMBJ-39-e103661-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/faa106320685/EMBJ-39-e103661-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/11faccf80064/EMBJ-39-e103661-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/f022e0e11a94/EMBJ-39-e103661-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/1da8248ca9e2/EMBJ-39-e103661-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/3dcd1cbf4764/EMBJ-39-e103661-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/215226cea139/EMBJ-39-e103661-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/0e2e694e2c4d/EMBJ-39-e103661-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/1fe9cd078ed2/EMBJ-39-e103661-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/ce733fe608b6/EMBJ-39-e103661-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/7737607/af994ac85ba6/EMBJ-39-e103661-g013.jpg

相似文献

1
Distinct retrograde microtubule motor sets drive early and late endosome transport.两种逆行微管马达分别驱动早期和晚期内涵体运输。
EMBO J. 2020 Dec 15;39(24):e103661. doi: 10.15252/embj.2019103661. Epub 2020 Nov 20.
2
Systems mapping of bidirectional endosomal transport through the crowded cell.双向内体运输在拥挤细胞中的系统映射。
Curr Biol. 2024 Oct 7;34(19):4476-4494.e11. doi: 10.1016/j.cub.2024.08.026. Epub 2024 Sep 13.
3
The role of microtubules and the dynein/dynactin motor complex of host cells in the biogenesis of the Coxiella burnetii-containing vacuole.宿主细胞微管和动力蛋白/动力蛋白激活蛋白复合物在包含柯克斯体的空泡生物发生中的作用。
PLoS One. 2019 Jan 14;14(1):e0209820. doi: 10.1371/journal.pone.0209820. eCollection 2019.
4
Transport of fungal RAB11 secretory vesicles involves myosin-5, dynein/dynactin/p25, and kinesin-1 and is independent of kinesin-3.真菌RAB11分泌囊泡的运输涉及肌球蛋白-5、动力蛋白/动力蛋白激活蛋白/p25和驱动蛋白-1，且不依赖于驱动蛋白-3。
Mol Biol Cell. 2017 Apr 1;28(7):947-961. doi: 10.1091/mbc.E16-08-0566. Epub 2017 Feb 16.
5
Cytoplasmic dynein and early endosome transport.细胞质动力蛋白与早期内体运输。
Cell Mol Life Sci. 2015 Sep;72(17):3267-80. doi: 10.1007/s00018-015-1926-y. Epub 2015 May 23.
6
Hook3 is a scaffold for the opposite-polarity microtubule-based motors cytoplasmic dynein-1 and KIF1C.Hook3 是一种支架，用于相反极性的微管基马达细胞质动力蛋白-1 和 KIF1C。
J Cell Biol. 2019 Sep 2;218(9):2982-3001. doi: 10.1083/jcb.201812170. Epub 2019 Jul 18.
7
A dynein loading zone for retrograde endosome motility at microtubule plus-ends.微管正端用于逆向内体运动的动力蛋白装载区。
EMBO J. 2006 Jun 7;25(11):2275-86. doi: 10.1038/sj.emboj.7601119. Epub 2006 May 11.
8
Role of dynactin in endocytic traffic: effects of dynamitin overexpression and colocalization with CLIP-170.动力蛋白激活蛋白在内吞运输中的作用：动力蛋白抑制蛋白过表达及与CLIP-170共定位的影响
Mol Biol Cell. 1999 Dec;10(12):4107-20. doi: 10.1091/mbc.10.12.4107.
9
Repeated ER-endosome contacts promote endosome translocation and neurite outgrowth.反复的内质网-内体接触促进内体转运和神经突生长。
Nature. 2015 Apr 9;520(7546):234-8. doi: 10.1038/nature14359.
10
Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L, and the receptor betalll spectrin.通过Rab7-RILP-p150Glued、ORP1L和受体βIII血影蛋白的逐步组装激活内体动力蛋白马达。
J Cell Biol. 2007 Feb 12;176(4):459-71. doi: 10.1083/jcb.200606077. Epub 2007 Feb 5.

引用本文的文献

1
Fibroblast IRF7-mediated chondrocyte apoptosis affects the progression of collapse in steroid-induced osteonecrosis of the femoral head.成纤维细胞IRF7介导的软骨细胞凋亡影响激素性股骨头坏死塌陷的进展。
J Orthop Surg Res. 2025 Mar 18;20(1):292. doi: 10.1186/s13018-025-05557-x.
2
Optogenetic control of kinesin-1, -2, -3 and dynein reveals their specific roles in vesicular transport.光遗传学控制驱动蛋白-1、-2、-3 和动力蛋白，揭示它们在囊泡运输中的特定作用。
Cell Rep. 2024 Aug 27;43(8):114649. doi: 10.1016/j.celrep.2024.114649. Epub 2024 Aug 18.
3
Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy.

本文引用的文献

1
Conformational diversity of dynactin sidearm and domain organization of its subunit p150.动力蛋白激活蛋白侧臂构象多样性及其亚基 p150 的结构域组织。
Mol Biol Cell. 2020 Jun 1;31(12):1218-1231. doi: 10.1091/mbc.E20-01-0031. Epub 2020 Apr 2.
2
Axonal precursor miRNAs hitchhike on endosomes and locally regulate the development of neural circuits.轴突前体 microRNAs 搭乘内体并局部调节神经回路的发育。
EMBO J. 2020 Mar 16;39(6):e102513. doi: 10.15252/embj.2019102513. Epub 2020 Feb 19.
3
mTOR at the nexus of nutrition, growth, ageing and disease.
HOOK1 水平维持的蛋白质内稳性通过内质网应激和自噬促进卵巢癌细胞的致瘤和干性特性。
J Exp Clin Cancer Res. 2024 May 29;43(1):150. doi: 10.1186/s13046-024-03071-2.
4
Septin-coated microtubules promote maturation of multivesicular bodies by inhibiting their motility.被 septin 包裹的微管通过抑制多泡体的运动来促进其成熟。
J Cell Biol. 2024 Aug 5;223(8). doi: 10.1083/jcb.202308049. Epub 2024 Apr 26.
5
Cytomembrane Trafficking Pathways of Connexin 26, 30, and 43.间隙连接蛋白 26、30 和 43 的细胞内膜转运途径。
Int J Mol Sci. 2023 Jun 19;24(12):10349. doi: 10.3390/ijms241210349.
6
Disruption of axonal transport in neurodegeneration.神经退行性疾病中轴突运输的中断。
J Clin Invest. 2023 Jun 1;133(11):e168554. doi: 10.1172/JCI168554.
7
Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes.卡兹林促进了从早期内体到再循环内体的依赖动力蛋白/动力蛋白激活蛋白复合物的运输。
Elife. 2023 Apr 25;12:e83793. doi: 10.7554/eLife.83793.
8
The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein.减数分裂 LINC 复合物组件 KASH5 是细胞质动力蛋白的激活接头。
J Cell Biol. 2023 May 1;222(5). doi: 10.1083/jcb.202204042. Epub 2023 Mar 22.
9
Drug Repurposing: The Mechanisms and Signaling Pathways of Anti-Cancer Effects of Anesthetics.药物再利用：麻醉剂抗癌作用的机制和信号通路
Biomedicines. 2022 Jul 4;10(7):1589. doi: 10.3390/biomedicines10071589.
10
The ciliopathy protein CCDC66 controls mitotic progression and cytokinesis by promoting microtubule nucleation and organization.纤毛病蛋白 CCDC66 通过促进微管的成核和组织来控制有丝分裂的进程和胞质分裂。
PLoS Biol. 2022 Jul 18;20(7):e3001708. doi: 10.1371/journal.pbio.3001708. eCollection 2022 Jul.
mTOR 在营养、生长、衰老和疾病的交汇点。
Nat Rev Mol Cell Biol. 2020 Apr;21(4):183-203. doi: 10.1038/s41580-019-0199-y. Epub 2020 Jan 14.
4
Lysosomes as dynamic regulators of cell and organismal homeostasis.溶酶体作为细胞和整体内稳态的动态调节剂。
Nat Rev Mol Cell Biol. 2020 Feb;21(2):101-118. doi: 10.1038/s41580-019-0185-4. Epub 2019 Nov 25.
5
Hook3 is a scaffold for the opposite-polarity microtubule-based motors cytoplasmic dynein-1 and KIF1C.Hook3 是一种支架，用于相反极性的微管基马达细胞质动力蛋白-1 和 KIF1C。
J Cell Biol. 2019 Sep 2;218(9):2982-3001. doi: 10.1083/jcb.201812170. Epub 2019 Jul 18.
6
PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport.PTPN21 和 Hook3 解除 KIF1C 的自动抑制并激活细胞内运输。
Nat Commun. 2019 Jun 19;10(1):2693. doi: 10.1038/s41467-019-10644-9.
7
Motor-cargo adaptors at the organelle-cytoskeleton interface.细胞器-细胞骨架界面的运动货物衔接器。
Curr Opin Cell Biol. 2019 Aug;59:16-23. doi: 10.1016/j.ceb.2019.02.010. Epub 2019 Apr 2.
8
A chemoproteomic portrait of the oncometabolite fumarate.富马酸盐的化学生物组学特征图谱
Nat Chem Biol. 2019 Apr;15(4):391-400. doi: 10.1038/s41589-018-0217-y. Epub 2019 Feb 4.
9
Dynein activator Hook1 is required for trafficking of BDNF-signaling endosomes in neurons.动力蛋白激活蛋白 Hook1 对于神经元中 BDNF 信号内体的运输是必需的。
J Cell Biol. 2019 Jan 7;218(1):220-233. doi: 10.1083/jcb.201805016. Epub 2018 Oct 29.
10
Innate Immune Signals Induce Anterograde Endosome Transport Promoting MHC Class I Cross-Presentation.先天免疫信号诱导顺行内体运输促进 MHC I 类交叉呈递。
Cell Rep. 2018 Sep 25;24(13):3568-3581. doi: 10.1016/j.celrep.2018.08.041.