• 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

Rab21 调节网格蛋白介导的内吞运输以促进未成熟神经突修剪。

Rab21 regulates caveolin-1-mediated endocytic trafficking to promote immature neurite pruning.

机构信息

Department of Physiology, Keio University School of Medicine, Tokyo, Japan.

Department of Aging Science and Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

出版信息

EMBO Rep. 2023 Mar 6;24(3):e54701. doi: 10.15252/embr.202254701. Epub 2023 Jan 23.

DOI:10.15252/embr.202254701
PMID:36683567
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9986827/
Abstract

Transmembrane proteins are internalized by clathrin- and caveolin-dependent endocytosis. Both pathways converge on early endosomes and are thought to share the small GTPase Rab5 as common regulator. In contrast to this notion, we show here that the clathrin- and caveolin-mediated endocytic pathways are differentially regulated. Rab5 and Rab21 localize to distinct populations of early endosomes in cortical neurons and preferentially regulate clathrin- and caveolin-mediated pathways, respectively, suggesting heterogeneity in the early endosomes, rather than a converging point. Suppression of Rab21, but not Rab5, results in decreased plasma membrane localization and total protein levels of caveolin-1, which perturbs immature neurite pruning of cortical neurons, an in vivo-specific step of neuronal maturation. Taken together, our data indicate that clathrin- and caveolin-mediated endocytic pathways run in parallel in early endosomes, which show different molecular regulation and physiological function.

摘要

跨膜蛋白通过网格蛋白和小窝蛋白依赖的内吞作用被内化。这两种途径都集中在早期内涵体上，并被认为共享小 GTPase Rab5 作为共同调节剂。与这一观点相反，我们在这里表明，网格蛋白和小窝蛋白介导的内吞途径受到不同的调节。Rab5 和 Rab21 在皮质神经元中的早期内涵体的不同群体中定位，并分别优先调节网格蛋白和小窝蛋白介导的途径，这表明早期内涵体存在异质性，而不是汇聚点。抑制 Rab21，但不抑制 Rab5，导致小窝蛋白-1 的质膜定位和总蛋白水平降低，这扰乱了皮质神经元不成熟突起的修剪，这是神经元成熟的一个体内特异性步骤。总之，我们的数据表明，网格蛋白和小窝蛋白介导的内吞途径在早期内涵体中平行运行，它们表现出不同的分子调节和生理功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/a283716ae552/EMBR-24-e54701-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/1ebb00746b6d/EMBR-24-e54701-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/9d15e3fd7797/EMBR-24-e54701-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/b74b9d69d4ca/EMBR-24-e54701-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/eec81ca7ba07/EMBR-24-e54701-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/f324a309dee6/EMBR-24-e54701-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/5a1e9a7c7d34/EMBR-24-e54701-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/6132dc1a3d87/EMBR-24-e54701-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/ad0ab91c8ae3/EMBR-24-e54701-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/d0c8c233aecf/EMBR-24-e54701-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/e944dc0caed8/EMBR-24-e54701-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/e3e57afd5570/EMBR-24-e54701-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/a283716ae552/EMBR-24-e54701-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/1ebb00746b6d/EMBR-24-e54701-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/9d15e3fd7797/EMBR-24-e54701-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/b74b9d69d4ca/EMBR-24-e54701-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/eec81ca7ba07/EMBR-24-e54701-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/f324a309dee6/EMBR-24-e54701-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/5a1e9a7c7d34/EMBR-24-e54701-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/6132dc1a3d87/EMBR-24-e54701-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/ad0ab91c8ae3/EMBR-24-e54701-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/d0c8c233aecf/EMBR-24-e54701-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/e944dc0caed8/EMBR-24-e54701-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/e3e57afd5570/EMBR-24-e54701-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd5/9986827/a283716ae552/EMBR-24-e54701-g009.jpg

相似文献

1
Rab21 regulates caveolin-1-mediated endocytic trafficking to promote immature neurite pruning.Rab21 调节网格蛋白介导的内吞运输以促进未成熟神经突修剪。
EMBO Rep. 2023 Mar 6;24(3):e54701. doi: 10.15252/embr.202254701. Epub 2023 Jan 23.
2
Internalization of the TGF-β type I receptor into caveolin-1 and EEA1 double-positive early endosomes.转化生长因子-βⅠ型受体内化进入小窝蛋白-1和早期内体抗原1双阳性的早期内体。
Cell Res. 2015 Jun;25(6):738-52. doi: 10.1038/cr.2015.60. Epub 2015 May 22.
3
Entry of Classical Swine Fever Virus into PK-15 Cells via a pH-, Dynamin-, and Cholesterol-Dependent, Clathrin-Mediated Endocytic Pathway That Requires Rab5 and Rab7.经典猪瘟病毒通过一种依赖于pH值、发动蛋白和胆固醇、由网格蛋白介导且需要Rab5和Rab7的内吞途径进入PK - 15细胞。
J Virol. 2016 Sep 29;90(20):9194-208. doi: 10.1128/JVI.00688-16. Print 2016 Oct 15.
4
Endocytosis and transcytosis in growing astrocytes in primary culture. Possible implications in neural development.原代培养中生长的星形胶质细胞的内吞作用和转胞吞作用。对神经发育的可能影响。
Int J Dev Biol. 2000 Feb;44(2):209-21.
5
Echovirus 7 entry into polarized intestinal epithelial cells requires clathrin and Rab7.肠道病毒 7 进入极化的肠上皮细胞需要网格蛋白和 Rab7。
mBio. 2012 Apr 10;3(2). doi: 10.1128/mBio.00304-11. Print 2012.
6
Selective membrane recruitment of EEA1 suggests a role in directional transport of clathrin-coated vesicles to early endosomes.EEA1的选择性膜募集表明其在网格蛋白包被囊泡向早期内体的定向运输中发挥作用。
J Biol Chem. 2000 Feb 11;275(6):3745-8. doi: 10.1074/jbc.275.6.3745.
7
Invasion of host cells by JC virus identifies a novel role for caveolae in endosomal sorting of noncaveolar ligands.JC病毒对宿主细胞的侵袭揭示了小窝在非小窝配体内体分选过程中的新作用。
J Virol. 2006 Oct;80(19):9402-13. doi: 10.1128/JVI.01086-06.
8
ALS2, the small GTPase Rab17-interacting protein, regulates maturation and sorting of Rab17-associated endosomes.ALS2，一种小 GTPase Rab17 相互作用蛋白，调节 Rab17 相关内体的成熟和分拣。
Biochem Biophys Res Commun. 2020 Mar 19;523(4):908-915. doi: 10.1016/j.bbrc.2019.12.122. Epub 2020 Jan 17.
9
The endocytic pathway taken by cationic substances requires Rab14 but not Rab5 and Rab7.阳离子物质所采用的内吞途径需要 Rab14，但不需要 Rab5 和 Rab7。
Cell Rep. 2021 Nov 2;37(5):109945. doi: 10.1016/j.celrep.2021.109945.
10
Altered TGF-β endocytic trafficking contributes to the increased signaling in Marfan syndrome.TGF-β 内吞运输的改变导致马凡综合征中信号的增加。
Biochim Biophys Acta Mol Basis Dis. 2018 Feb;1864(2):554-562. doi: 10.1016/j.bbadis.2017.11.015. Epub 2017 Nov 23.

引用本文的文献

1
Rab21 recruits EEA1 and competes with Rab5 for Rabex-5 activation.Rab21招募EEA1并与Rab5竞争以激活Rabex-5。
Front Cell Dev Biol. 2025 May 30;13:1588308. doi: 10.3389/fcell.2025.1588308. eCollection 2025.
2
Caveolae-Mediated Transcytosis and Its Role in Neurological Disorders.小窝介导的转胞吞作用及其在神经系统疾病中的作用。
Biomolecules. 2025 Mar 21;15(4):456. doi: 10.3390/biom15040456.
3
Roles of N-cadherin in cerebral cortical development: cooperation with membrane trafficking and actin cytoskeletal regulation.

本文引用的文献

1
Unconventional endocytic mechanisms.非常规内吞作用机制。
Curr Opin Cell Biol. 2021 Aug;71:120-129. doi: 10.1016/j.ceb.2021.03.001. Epub 2021 Apr 13.
2
Inhibition of clathrin-mediated endocytosis by knockdown of AP-2 leads to alterations in the plasma membrane proteome.通过敲低 AP-2 抑制网格蛋白介导的内吞作用会导致质膜蛋白质组发生改变。
Traffic. 2021 Jan;22(1-2):6-22. doi: 10.1111/tra.12770. Epub 2020 Dec 18.
3
Correlative single-molecule localization microscopy and electron tomography reveals endosome nanoscale domains.
N-钙黏蛋白在大脑皮质发育中的作用：与膜转运和肌动蛋白细胞骨架调节的协同作用
Neural Regen Res. 2025 Jan 1;20(1):188-190. doi: 10.4103/NRR.NRR-D-23-02069. Epub 2024 Apr 3.
4
Genome assemblies for (Teleostei: Cichlidae) identify a novel candidate gene for vertebrate sex determination, RIN3.硬骨鱼纲（辐鳍鱼亚纲：丽鱼科）的基因组组装鉴定出一个脊椎动物性别决定的新候选基因，即RIN3。
Front Genet. 2024 Aug 16;15:1447628. doi: 10.3389/fgene.2024.1447628. eCollection 2024.
5
Membrane remodeling by FAM92A1 during brain development regulates neuronal morphology, synaptic function, and cognition.在大脑发育过程中，FAM92A1 通过膜重塑调节神经元形态、突触功能和认知。
Nat Commun. 2024 Jul 23;15(1):6209. doi: 10.1038/s41467-024-50565-w.
6
Robust GRK2/3/6-dependent desensitization of oxytocin receptor in neurons.神经元中依赖GRK2/3/6的催产素受体的强大脱敏作用。
iScience. 2024 May 22;27(6):110047. doi: 10.1016/j.isci.2024.110047. eCollection 2024 Jun 21.
7
Exchangeable leaders of collectively migrating glioma abuse N-cadherin trafficking.集体迁移的胶质瘤的可交换领导者滥用N-钙黏蛋白运输。
J Cell Biol. 2024 Jun 3;223(6). doi: 10.1083/jcb.202404129. Epub 2024 May 3.
8
Immunocytochemistry of Primary Cultured Cerebral Cortical Neurons.原代大脑皮质神经元的免疫细胞化学。
Methods Mol Biol. 2024;2794:177-186. doi: 10.1007/978-1-0716-3810-1_15.
9
Primary Culture of Dissociated Neurons from the Embryonic Cerebral Cortex.胚胎大脑皮质分离神经元的原代培养。
Methods Mol Biol. 2024;2794:169-175. doi: 10.1007/978-1-0716-3810-1_14.
10
Vesicular Trafficking, a Mechanism Controlled by Cascade Activation of Rab Proteins: Focus on Rab27.囊泡运输：一种由Rab蛋白级联激活控制的机制——聚焦于Rab27
Biology (Basel). 2023 Dec 15;12(12):1530. doi: 10.3390/biology12121530.
相关单分子定位显微镜和电子断层扫描揭示了内涵体的纳米尺度结构域。
Traffic. 2019 Aug;20(8):601-617. doi: 10.1111/tra.12671.
4
APEX2-mediated RAB proximity labeling identifies a role for RAB21 in clathrin-independent cargo sorting.APEX2 介导的 RAB 临近标记鉴定了 RAB21 在网格蛋白非依赖的货物分拣中的作用。
EMBO Rep. 2019 Feb;20(2). doi: 10.15252/embr.201847192. Epub 2019 Jan 3.
5
Caveolae: Structure, Function, and Relationship to Disease.陷窝小体：结构、功能及其与疾病的关系。
Annu Rev Cell Dev Biol. 2018 Oct 6;34:111-136. doi: 10.1146/annurev-cellbio-100617-062737.
6
Caveolin-1 Promotes Early Neuronal Maturation via Caveolae-Independent Trafficking of N-Cadherin and L1.小窝蛋白-1通过非小窝依赖的N-钙黏蛋白和L1转运促进神经元早期成熟。
iScience. 2018 Sep 28;7:53-67. doi: 10.1016/j.isci.2018.08.014. Epub 2018 Aug 21.
7
The Ankrd13 Family of Ubiquitin-interacting Motif-bearing Proteins Regulates Valosin-containing Protein/p97 Protein-mediated Lysosomal Trafficking of Caveolin 1.含泛素相互作用基序的Ankrd13蛋白家族调控含缬酪肽蛋白/p97蛋白介导的小窝蛋白1的溶酶体运输。
J Biol Chem. 2016 Mar 18;291(12):6218-31. doi: 10.1074/jbc.M115.710707. Epub 2016 Jan 21.
8
Cellullar insights into cerebral cortical development: focusing on the locomotion mode of neuronal migration.对大脑皮质发育的细胞层面见解：聚焦神经元迁移的运动模式。
Front Cell Neurosci. 2015 Oct 7;9:394. doi: 10.3389/fncel.2015.00394. eCollection 2015.
9
APPL endosomes are not obligatory endocytic intermediates but act as stable cargo-sorting compartments.APPL内体不是必需的内吞中间体，而是作为稳定的货物分拣区室发挥作用。
J Cell Biol. 2015 Oct 12;211(1):123-44. doi: 10.1083/jcb.201311117.
10
Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids.动态小窝排除大量膜蛋白，是过量糖鞘脂分选所必需的。
Nat Commun. 2015 Apr 21;6:6867. doi: 10.1038/ncomms7867.