• 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

Vav 通过不同的基于肌动蛋白的过程独立调节突触生长和可塑性。

Vav independently regulates synaptic growth and plasticity through distinct actin-based processes.

机构信息

Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea.

Department of Cell and Developmental Biology and Dental Research Institute, Seoul National University, Seoul, Korea.

出版信息

J Cell Biol. 2022 Oct 3;221(10). doi: 10.1083/jcb.202203048. Epub 2022 Aug 17.

DOI:10.1083/jcb.202203048
PMID:35976098
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9388202/
Abstract

Modulation of presynaptic actin dynamics is fundamental to synaptic growth and functional plasticity; yet the underlying molecular and cellular mechanisms remain largely unknown. At Drosophila NMJs, the presynaptic Rac1-SCAR pathway mediates BMP-induced receptor macropinocytosis to inhibit BMP growth signaling. Here, we show that the Rho-type GEF Vav acts upstream of Rac1 to inhibit synaptic growth through macropinocytosis. We also present evidence that Vav-Rac1-SCAR signaling has additional roles in tetanus-induced synaptic plasticity. Presynaptic inactivation of Vav signaling pathway components, but not regulators of macropinocytosis, impairs post-tetanic potentiation (PTP) and enhances synaptic depression depending on external Ca2+ concentration. Interfering with the Vav-Rac1-SCAR pathway also impairs mobilization of reserve pool (RP) vesicles required for tetanus-induced synaptic plasticity. Finally, treatment with an F-actin-stabilizing drug completely restores RP mobilization and plasticity defects in Vav mutants. We propose that actin-regulatory Vav-Rac1-SCAR signaling independently regulates structural and functional presynaptic plasticity by driving macropinocytosis and RP mobilization, respectively.

摘要

突触前肌动蛋白动力学的调节对于突触生长和功能可塑性至关重要；然而，其潜在的分子和细胞机制在很大程度上仍不清楚。在果蝇 NMJs 中，突触前 Rac1-SCAR 途径介导 BMP 诱导的受体胞吞作用，以抑制 BMP 生长信号。在这里，我们表明 Rho 型 GEF Vav 作为 Rac1 的上游因子，通过胞吞作用抑制突触生长。我们还提供了证据表明，Vav-Rac1-SCAR 信号通路在破伤风诱导的突触可塑性中具有额外的作用。突触前 Vav 信号通路成分的失活，但不是胞吞作用的调节剂，会损害强直后增强（PTP），并根据外部 Ca2+浓度增强突触抑制。干扰 Vav-Rac1-SCAR 途径也会损害破伤风诱导的突触可塑性所需的储备池 (RP) 囊泡的动员。最后，用肌动蛋白稳定药物处理可完全恢复 Vav 突变体中 RP 的动员和可塑性缺陷。我们提出，肌动蛋白调节的 Vav-Rac1-SCAR 信号通路分别通过驱动胞吞作用和 RP 动员来独立调节结构和功能的突触可塑性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/be12517e375e/JCB_202203048_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/f85a8a30fdea/JCB_202203048_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/f6e31624f8c6/JCB_202203048_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/06c48ca51553/JCB_202203048_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/8c2a68f6a1a7/JCB_202203048_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/7b2d396dd97f/JCB_202203048_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/8064ff0677d7/JCB_202203048_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/9b962c5a0c88/JCB_202203048_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/4139402b4d82/JCB_202203048_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/bba57ac8df04/JCB_202203048_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/5c77358af01d/JCB_202203048_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/27b40e17a714/JCB_202203048_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/b79aea86fadf/JCB_202203048_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/d9e2178a676a/JCB_202203048_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/56c80e8c67e2/JCB_202203048_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/be12517e375e/JCB_202203048_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/f85a8a30fdea/JCB_202203048_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/f6e31624f8c6/JCB_202203048_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/06c48ca51553/JCB_202203048_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/8c2a68f6a1a7/JCB_202203048_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/7b2d396dd97f/JCB_202203048_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/8064ff0677d7/JCB_202203048_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/9b962c5a0c88/JCB_202203048_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/4139402b4d82/JCB_202203048_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/bba57ac8df04/JCB_202203048_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/5c77358af01d/JCB_202203048_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/27b40e17a714/JCB_202203048_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/b79aea86fadf/JCB_202203048_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/d9e2178a676a/JCB_202203048_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/56c80e8c67e2/JCB_202203048_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f4a/9388202/be12517e375e/JCB_202203048_Fig10.jpg

相似文献

1
Vav independently regulates synaptic growth and plasticity through distinct actin-based processes.Vav 通过不同的基于肌动蛋白的过程独立调节突触生长和可塑性。
J Cell Biol. 2022 Oct 3;221(10). doi: 10.1083/jcb.202203048. Epub 2022 Aug 17.
2
Presynaptic structural and functional plasticity are coupled by convergent Rap1 signaling.突触前结构和功能可塑性通过会聚的 Rap1 信号传递偶联。
J Cell Biol. 2024 Jul 1;223(7). doi: 10.1083/jcb.202309095. Epub 2024 May 15.
3
Retrograde BMP signaling modulates rapid activity-dependent synaptic growth via presynaptic LIM kinase regulation of cofilin.逆行 BMP 信号通过调节 LIM 激酶活性依赖性突触生长来调节 LIM 激酶活性。
J Neurosci. 2014 Mar 19;34(12):4371-81. doi: 10.1523/JNEUROSCI.4943-13.2014.
4
Formin-dependent synaptic growth: evidence that Dlar signals via Diaphanous to modulate synaptic actin and dynamic pioneer microtubules.依赖formin的突触生长：Dlar通过Diaphanous发出信号以调节突触肌动蛋白和动态先驱微管的证据。
J Neurosci. 2008 Oct 29;28(44):11111-23. doi: 10.1523/JNEUROSCI.0833-08.2008.
5
BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis.BMP 依赖性突触发育需要 BMP 受体巨胞饮作用的 Abi-Abl-Rac 信号转导。
Nat Commun. 2019 Feb 8;10(1):684. doi: 10.1038/s41467-019-08533-2.
6
Neuroligin 4 regulates synaptic growth via the bone morphogenetic protein (BMP) signaling pathway at the neuromuscular junction.神经连接蛋白4通过骨形态发生蛋白（BMP）信号通路在神经肌肉接头处调节突触生长。
J Biol Chem. 2017 Nov 3;292(44):17991-18005. doi: 10.1074/jbc.M117.810242. Epub 2017 Sep 14.
7
Synaptic homeostats: latent plasticity revealed at the Drosophila neuromuscular junction.突触稳态：在果蝇神经肌肉接点揭示的潜在可塑性。
Cell Mol Life Sci. 2021 Apr;78(7):3159-3179. doi: 10.1007/s00018-020-03732-3. Epub 2021 Jan 15.
8
Two synaptic vesicle pools, vesicle recruitment and replenishment of pools at the Drosophila neuromuscular junction.果蝇神经肌肉接头处的两个突触小泡池、小泡募集及池的补充
J Neurocytol. 2003 Jun-Sep;32(5-8):551-65. doi: 10.1023/B:NEUR.0000020610.13554.3c.
9
Action potential-coupled Rho GTPase signaling drives presynaptic plasticity.动作电位偶联 Rho GTPase 信号转导驱动突触前可塑性。
Elife. 2021 Jul 16;10:e63756. doi: 10.7554/eLife.63756.
10
Activity-Induced Synaptic Structural Modifications by an Activator of Integrin Signaling at the Neuromuscular Junction.整合素信号激活剂在神经肌肉接头处诱导的活动依赖性突触结构修饰
J Neurosci. 2017 Mar 22;37(12):3246-3263. doi: 10.1523/JNEUROSCI.3128-16.2017. Epub 2017 Feb 20.

引用本文的文献

1
CRISPR/Cas9 technology in the modeling of and evaluation of possible treatments for Niemann-Pick C.CRISPR/Cas9 技术在尼曼-匹克 C 型建模及潜在治疗方法评估中的应用
Mol Biol Rep. 2024 Jul 20;51(1):828. doi: 10.1007/s11033-024-09801-1.
2
Presynaptic structural and functional plasticity are coupled by convergent Rap1 signaling.突触前结构和功能可塑性通过会聚的 Rap1 信号传递偶联。
J Cell Biol. 2024 Jul 1;223(7). doi: 10.1083/jcb.202309095. Epub 2024 May 15.
3
The planar cell polarity pathway is essential for optimal activity-dependent synaptic plasticity.

本文引用的文献

1
Multiple Roles of Actin in Exo- and Endocytosis.肌动蛋白在胞吐作用和胞吞作用中的多种作用。
Front Synaptic Neurosci. 2022 Mar 4;14:841704. doi: 10.3389/fnsyn.2022.841704. eCollection 2022.
2
ALS2 regulates endosomal trafficking, postsynaptic development, and neuronal survival.ALS2调节内体运输、突触后发育和神经元存活。
J Cell Biol. 2021 May 3;220(5). doi: 10.1083/jcb.202007112.
3
Homeostatic control of Drosophila neuromuscular junction function.果蝇神经肌肉接点功能的动态平衡控制。
平面细胞极性通路对于最佳的活动依赖性突触可塑性至关重要。
Front Synaptic Neurosci. 2024 Apr 3;16:1322771. doi: 10.3389/fnsyn.2024.1322771. eCollection 2024.
4
CYRI proteins: controllers of actin dynamics in the cellular 'eat vs walk' decision.CYRI 蛋白：细胞“吃还是走”决策中控制肌动蛋白动态的控制器。
Biochem Soc Trans. 2023 Apr 26;51(2):579-585. doi: 10.1042/BST20221354.
5
Compromised osteogenic effect of exosomes internalized by senescent bone marrow stem cells endocytoses involving clathrin, macropinocytosis and caveolae.衰老骨髓干细胞内化的外泌体的成骨作用受损，其内化过程涉及网格蛋白、巨胞饮作用和小窝。
Front Bioeng Biotechnol. 2023 Jan 4;10:1090914. doi: 10.3389/fbioe.2022.1090914. eCollection 2022.
Synapse. 2020 Jan;74(1):e22133. doi: 10.1002/syn.22133. Epub 2019 Oct 4.
4
BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis.BMP 依赖性突触发育需要 BMP 受体巨胞饮作用的 Abi-Abl-Rac 信号转导。
Nat Commun. 2019 Feb 8;10(1):684. doi: 10.1038/s41467-019-08533-2.
5
The functional architecture of axonal actin.轴突肌动蛋白的功能结构。
Mol Cell Neurosci. 2018 Sep;91:151-159. doi: 10.1016/j.mcn.2018.05.003. Epub 2018 May 12.
6
A Ca2+ channel differentially regulates Clathrin-mediated and activity-dependent bulk endocytosis.一种钙离子通道对网格蛋白介导的内吞作用和活性依赖的批量内吞作用具有差异性调节作用。
PLoS Biol. 2017 Apr 17;15(4):e2000931. doi: 10.1371/journal.pbio.2000931. eCollection 2017 Apr.
7
Phosphorylation of Synaptojanin Differentially Regulates Endocytosis of Functionally Distinct Synaptic Vesicle Pools.突触结合蛋白的磷酸化差异调节功能不同的突触小泡池的内吞作用。
J Neurosci. 2016 Aug 24;36(34):8882-94. doi: 10.1523/JNEUROSCI.1470-16.2016.
8
Relevance of presynaptic actin dynamics for synapse function and mouse behavior.突触前肌动蛋白动力学对突触功能和小鼠行为的相关性。
Exp Cell Res. 2015 Jul 15;335(2):165-71. doi: 10.1016/j.yexcr.2014.12.020. Epub 2015 Jan 8.
9
Retrograde BMP signaling at the synapse: a permissive signal for synapse maturation and activity-dependent plasticity.突触中的逆行 BMP 信号：促进突触成熟和活动依赖性可塑性的许可信号。
J Neurosci. 2013 Nov 6;33(45):17937-50. doi: 10.1523/JNEUROSCI.6075-11.2013.
10
Development and plasticity of the Drosophila larval neuromuscular junction.果蝇幼虫神经肌肉接头的发育与可塑性。
Wiley Interdiscip Rev Dev Biol. 2013 Sep-Oct;2(5):647-70. doi: 10.1002/wdev.108. Epub 2013 Feb 5.