• 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

由ADF/丝切蛋白介导的囊泡运输对乙酰胆碱受体聚集的调控

Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking.

作者信息

Lee Chi Wai, Han Jianzhong, Bamburg James R, Han Liang, Lynn Rachel, Zheng James Q

机构信息

Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA.

出版信息

Nat Neurosci. 2009 Jul;12(7):848-56. doi: 10.1038/nn.2322. Epub 2009 May 31.

DOI:10.1038/nn.2322
PMID:19483689
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2714269/
Abstract

Postsynaptic receptor localization is crucial for synapse development and function, but the underlying cytoskeletal mechanisms remain elusive. Using Xenopus neuromuscular junctions as a model, we found that actin depolymerizing factor (ADF)/cofilin regulated actin-dependent vesicular trafficking of acetylcholine receptors (AChRs) to the postsynaptic membrane. Active ADF/cofilin was concentrated in small puncta adjacent to AChR clusters and was spatiotemporally correlated with the formation and maintenance of surface AChR clusters. Notably, increased actin dynamics, vesicular markers and intracellular AChRs were all enriched at the sites of ADF/cofilin localization. Furthermore, a substantial amount of new AChRs was detected at these ADF/cofilin-enriched sites. Manipulation of either ADF/cofilin activity through its serine-3 phosphorylation or ADF/cofilin localization via 14-3-3 proteins markedly attenuated AChR insertion and clustering. These results suggest that spatiotemporally restricted ADF/cofilin-mediated actin dynamics regulate AChR trafficking during the development of neuromuscular synapses.

摘要

突触后受体定位对于突触的发育和功能至关重要，但其潜在的细胞骨架机制仍不清楚。以非洲爪蟾神经肌肉接头为模型，我们发现肌动蛋白解聚因子（ADF）/丝切蛋白调节乙酰胆碱受体（AChR）依赖肌动蛋白的囊泡运输至突触后膜。活性ADF/丝切蛋白集中在与AChR簇相邻的小斑点中，并且在时空上与表面AChR簇的形成和维持相关。值得注意的是，增加的肌动蛋白动力学、囊泡标记物和细胞内AChR均在ADF/丝切蛋白定位的位点富集。此外，在这些富含ADF/丝切蛋白的位点检测到大量新的AChR。通过其丝氨酸-3磷酸化对ADF/丝切蛋白活性进行操纵，或通过14-3-3蛋白对ADF/丝切蛋白定位进行操纵，均显著减弱AChR插入和聚集。这些结果表明，在神经肌肉突触发育过程中，时空受限的ADF/丝切蛋白介导的肌动蛋白动力学调节AChR运输。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/816938e674a5/nihms105921f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/e0fb83f7e3ff/nihms105921f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/dbb4c3b6b035/nihms105921f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/2da1810492f4/nihms105921f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/ad8349bed75a/nihms105921f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/948dbcf97090/nihms105921f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/b341811b8aa7/nihms105921f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/28c1b8dde3d9/nihms105921f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/816938e674a5/nihms105921f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/e0fb83f7e3ff/nihms105921f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/dbb4c3b6b035/nihms105921f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/2da1810492f4/nihms105921f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/ad8349bed75a/nihms105921f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/948dbcf97090/nihms105921f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/b341811b8aa7/nihms105921f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/28c1b8dde3d9/nihms105921f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e5/2714269/816938e674a5/nihms105921f8.jpg

相似文献

1
Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking.由ADF/丝切蛋白介导的囊泡运输对乙酰胆碱受体聚集的调控
Nat Neurosci. 2009 Jul;12(7):848-56. doi: 10.1038/nn.2322. Epub 2009 May 31.
2
Grp94 Regulates the Recruitment of Aneural AChR Clusters for the Assembly of Postsynaptic Specializations by Modulating ADF/Cofilin Activity and Turnover.Grp94 通过调节 ADF/Cofilin 的活性和周转来调节无神经 AChR 簇的募集，用于形成突触后特化。
eNeuro. 2020 Sep 8;7(5). doi: 10.1523/ENEURO.0025-20.2020. Print 2020 Sep/Oct.
3
Using Xenopus tissue cultures for the study of myasthenia gravis pathogenesis.利用非洲爪蟾组织培养研究重症肌无力的发病机制。
Dev Biol. 2015 Dec 15;408(2):244-51. doi: 10.1016/j.ydbio.2015.02.017. Epub 2015 Mar 3.
4
CLASP2-dependent microtubule capture at the neuromuscular junction membrane requires LL5β and actin for focal delivery of acetylcholine receptor vesicles.在神经肌肉接头膜处，依赖CLASP2的微管捕获需要LL5β和肌动蛋白来实现乙酰胆碱受体囊泡的局部递送。
Mol Biol Cell. 2015 Mar 1;26(5):938-51. doi: 10.1091/mbc.E14-06-1158. Epub 2015 Jan 14.
5
ADF/Cofilin Controls Synaptic Actin Dynamics and Regulates Synaptic Vesicle Mobilization and Exocytosis.肌动蛋白解聚因子/丝切蛋白调控突触肌动蛋白动力学，并调节突触小泡的动员与胞吐作用。
Cereb Cortex. 2015 Sep;25(9):2863-75. doi: 10.1093/cercor/bhu081. Epub 2014 Apr 25.
6
ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity.ADF/cofilin 介导的肌动蛋白动力学调节突触可塑性过程中 AMPA 受体的运输。
Nat Neurosci. 2010 Oct;13(10):1208-15. doi: 10.1038/nn.2634. Epub 2010 Sep 12.
7
The function of cortactin in the clustering of acetylcholine receptors at the vertebrate neuromuscular junction.在脊椎动物神经肌肉接头处，桩蛋白在乙酰胆碱受体聚集中的功能。
PLoS One. 2009 Dec 29;4(12):e8478. doi: 10.1371/journal.pone.0008478.
8
Involvement of slingshot in the Rho-mediated dephosphorylation of ADF/cofilin during Xenopus cleavage.在非洲爪蟾卵裂过程中，弹弓蛋白参与Rho介导的ADF/丝切蛋白去磷酸化作用。
Zoolog Sci. 2005 Sep;22(9):971-84. doi: 10.2108/zsj.22.971.
9
Agrin triggers the clustering of raft-associated acetylcholine receptors through actin cytoskeleton reorganization.Agrin 通过肌动蛋白细胞骨架重组触发筏相关乙酰胆碱受体的聚集。
Biol Cell. 2011 Jun;103(6):287-301. doi: 10.1042/BC20110018.
10
N-cofilin can compensate for the loss of ADF in excitatory synapses.N-肌动蛋白结合蛋白（N-cofilin）可弥补兴奋性突触中 ADF 的缺失。
PLoS One. 2011;6(10):e26789. doi: 10.1371/journal.pone.0026789. Epub 2011 Oct 28.

引用本文的文献

1
Localized release of muscle-generated BDNF regulates the initial formation of postsynaptic apparatus at neuromuscular synapses.肌肉产生的脑源性神经营因子的局部释放调节神经肌肉突触处突触后装置的初始形成。
Cell Death Differ. 2025 Mar;32(3):546-560. doi: 10.1038/s41418-024-01404-4. Epub 2024 Nov 7.
2
Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission.肌动蛋白丝结合蛋白改变神经肌肉接头的突触后发育，从而增强功能性神经递质传递。
Development. 2024 Jul 1;151(13). doi: 10.1242/dev.202558. Epub 2024 Jul 8.
3
Alteration of actin cytoskeletal organisation in fetal akinesia deformation sequence.

本文引用的文献

1
Rapsyn interaction with calpain stabilizes AChR clusters at the neuromuscular junction.rapsyn与钙蛋白酶的相互作用可稳定神经肌肉接头处的乙酰胆碱受体簇。
Neuron. 2007 Jul 19;55(2):247-60. doi: 10.1016/j.neuron.2007.06.031.
2
BMP gradients steer nerve growth cones by a balancing act of LIM kinase and Slingshot phosphatase on ADF/cofilin.骨形态发生蛋白梯度通过LIM激酶和弹弓磷酸酶对肌动蛋白解聚因子/丝切蛋白的平衡作用引导神经生长锥。
J Cell Biol. 2007 Jul 2;178(1):107-19. doi: 10.1083/jcb.200703055.
3
Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin.
胎儿运动障碍性序列中肌动蛋白细胞骨架结构的改变。
Sci Rep. 2024 Jan 19;14(1):1742. doi: 10.1038/s41598-023-50615-1.
4
Nerve-independent formation of membrane infoldings at topologically complex postsynaptic apparatus by caveolin-3.网格蛋白-3 介导的拓扑结构复杂的突触后装置中神经独立性的膜内陷形成。
Sci Adv. 2023 Jun 16;9(24):eadg0183. doi: 10.1126/sciadv.adg0183.
5
14-3-3θ Does Not Protect against Behavioral or Pathological Deficits in Alzheimer's Disease Mouse Models.14-3-3θ 不能预防阿尔茨海默病小鼠模型的行为或病理缺陷。
eNeuro. 2022 Jun 24;9(3). doi: 10.1523/ENEURO.0368-21.2022. Print 2022 May-Jun.
6
Motor unit recovery following Smn restoration in mouse models of spinal muscular atrophy.运动神经元在脊髓性肌萎缩症小鼠模型中 Smn 恢复后的恢复。
Hum Mol Genet. 2022 Sep 10;31(18):3107-3119. doi: 10.1093/hmg/ddac097.
7
Drebrin Regulates Acetylcholine Receptor Clustering and Organization of Microtubules at the Postsynaptic Machinery. drebrin 调节乙酰胆碱受体在突触后机制中的聚集和微管组织。
Int J Mol Sci. 2021 Aug 30;22(17):9387. doi: 10.3390/ijms22179387.
8
Maturation of a postsynaptic domain: Role of small Rho GTPases in organising nicotinic acetylcholine receptor aggregates at the vertebrate neuromuscular junction.突触后结构的成熟：小 Rho GTPases 在脊椎动物神经肌肉接头处乙酰胆碱受体聚集中的作用。
J Anat. 2022 Nov;241(5):1148-1156. doi: 10.1111/joa.13526. Epub 2021 Aug 3.
9
The Metabolic Stability of the Nicotinic Acetylcholine Receptor at the Neuromuscular Junction.神经肌肉接头处烟碱型乙酰胆碱受体的代谢稳定性。
Cells. 2021 Feb 9;10(2):358. doi: 10.3390/cells10020358.
10
Grp94 Regulates the Recruitment of Aneural AChR Clusters for the Assembly of Postsynaptic Specializations by Modulating ADF/Cofilin Activity and Turnover.Grp94 通过调节 ADF/Cofilin 的活性和周转来调节无神经 AChR 簇的募集，用于形成突触后特化。
eNeuro. 2020 Sep 8;7(5). doi: 10.1523/ENEURO.0025-20.2020. Print 2020 Sep/Oct.
在不同浓度的ADF/丝切蛋白作用下，通过切断和成核作用实现肌动蛋白丝周转的机制。
Mol Cell. 2006 Oct 6;24(1):13-23. doi: 10.1016/j.molcel.2006.08.006.
4
Organelles and trafficking machinery for postsynaptic plasticity.用于突触后可塑性的细胞器与运输机制。
Annu Rev Neurosci. 2006;29:325-62. doi: 10.1146/annurev.neuro.29.051605.112808.
5
A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells.LIM激酶1/丝切蛋白通路在调控人乳腺癌细胞中表皮生长因子受体的内吞运输中的作用。
Histochem Cell Biol. 2006 Nov;126(5):627-38. doi: 10.1007/s00418-006-0198-x. Epub 2006 Jun 9.
6
Differential role of 14-3-3 family members in Xenopus development.14-3-3家族成员在非洲爪蟾发育中的差异作用。
Dev Dyn. 2006 Jul;235(7):1761-76. doi: 10.1002/dvdy.20816.
7
Kiss-and-coat and compartment mixing: coupling exocytosis to signal generation and local actin assembly.亲吻与包裹以及区室混合：将胞吐作用与信号产生及局部肌动蛋白组装相偶联。
Mol Biol Cell. 2006 Apr;17(4):1495-502. doi: 10.1091/mbc.e05-10-0908. Epub 2006 Jan 25.
8
Spatial organization of cofilin in dendritic spines.丝状肌动蛋白结合蛋白在树突棘中的空间组织。
Neuroscience. 2006;138(2):447-56. doi: 10.1016/j.neuroscience.2005.11.025. Epub 2006 Jan 4.
9
Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter.集聚蛋白通过抵消神经递质的抑制作用来促进突触分化。
Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11088-93. doi: 10.1073/pnas.0504806102. Epub 2005 Jul 25.
10
Neurotransmitter acetylcholine negatively regulates neuromuscular synapse formation by a Cdk5-dependent mechanism.神经递质乙酰胆碱通过一种依赖细胞周期蛋白依赖性激酶5（Cdk5）的机制对神经肌肉突触的形成起负向调节作用。
Neuron. 2005 May 19;46(4):569-79. doi: 10.1016/j.neuron.2005.04.002.