• 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

一条PIK3C3-锚蛋白B-动力蛋白激活蛋白途径促进轴突生长和多细胞器运输。

A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport.

作者信息

Lorenzo Damaris Nadia, Badea Alexandra, Davis Jonathan, Hostettler Janell, He Jiang, Zhong Guisheng, Zhuang Xiaowei, Bennett Vann

机构信息

Howard Hughes Medical Institute, Chevy Chase, MD 20815 Department of Biochemistry and Department of Radiology, Duke University, Durham, NC 27708.

Department of Biochemistry and Department of Radiology, Duke University, Durham, NC 27708.

出版信息

J Cell Biol. 2014 Dec 22;207(6):735-52. doi: 10.1083/jcb.201407063.

DOI:10.1083/jcb.201407063
PMID:25533844
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4274267/
Abstract

Axon growth requires long-range transport of organelles, but how these cargoes recruit their motors and how their traffic is regulated are not fully resolved. In this paper, we identify a new pathway based on the class III PI3-kinase (PIK3C3), ankyrin-B (AnkB), and dynactin, which promotes fast axonal transport of synaptic vesicles, mitochondria, endosomes, and lysosomes. We show that dynactin associates with cargo through AnkB interactions with both the dynactin subunit p62 and phosphatidylinositol 3-phosphate (PtdIns(3)P) lipids generated by PIK3C3. AnkB knockout resulted in shortened axon tracts and marked reduction in membrane association of dynactin and dynein, whereas it did not affect the organization of spectrin-actin axonal rings imaged by 3D-STORM. Loss of AnkB or of its linkages to either p62 or PtdIns(3)P or loss of PIK3C3 all impaired organelle transport and particularly retrograde transport in hippocampal neurons. Our results establish new functional relationships between PIK3C3, dynactin, and AnkB that together promote axonal transport of organelles and are required for normal axon length.

摘要

轴突生长需要细胞器的长距离运输，但这些货物如何招募其动力蛋白以及它们的运输如何被调节尚未完全解决。在本文中，我们确定了一条基于III类磷脂酰肌醇3-激酶（PIK3C3）、锚蛋白B（AnkB）和动力蛋白激活蛋白的新途径，该途径促进突触小泡、线粒体、内体和溶酶体的快速轴突运输。我们表明，动力蛋白激活蛋白通过AnkB与动力蛋白激活蛋白亚基p62和PIK3C3产生的磷脂酰肌醇3-磷酸（PtdIns(3)P）脂质的相互作用与货物结合。AnkB基因敲除导致轴突束缩短，动力蛋白激活蛋白和动力蛋白的膜结合显著减少，而这并不影响通过3D-STORM成像的血影蛋白-肌动蛋白轴突环的组织。AnkB的缺失或其与p62或PtdIns(3)P的连接缺失或PIK3C3的缺失均损害了细胞器运输，尤其是海马神经元中的逆行运输。我们的结果建立了PIK3C3、动力蛋白激活蛋白和AnkB之间新的功能关系，它们共同促进细胞器的轴突运输，并且是正常轴突长度所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/e4f72c1c62b8/JCB_201407063_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/bf3c2df47a19/JCB_201407063_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/6b71cd1ef60d/JCB_201407063_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/35609d7ffc4c/JCB_201407063_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/6e16ea5e0b8a/JCB_201407063_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/2badff255011/JCB_201407063_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/1f3201932adf/JCB_201407063_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/451c1a372424/JCB_201407063_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/5ed750f29524/JCB_201407063_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/aa014c77977a/JCB_201407063_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/e4f72c1c62b8/JCB_201407063_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/bf3c2df47a19/JCB_201407063_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/6b71cd1ef60d/JCB_201407063_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/35609d7ffc4c/JCB_201407063_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/6e16ea5e0b8a/JCB_201407063_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/2badff255011/JCB_201407063_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/1f3201932adf/JCB_201407063_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/451c1a372424/JCB_201407063_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/5ed750f29524/JCB_201407063_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/aa014c77977a/JCB_201407063_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa4d/4274267/e4f72c1c62b8/JCB_201407063_Fig10.jpg

相似文献

1
A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport.一条PIK3C3-锚蛋白B-动力蛋白激活蛋白途径促进轴突生长和多细胞器运输。
J Cell Biol. 2014 Dec 22;207(6):735-52. doi: 10.1083/jcb.201407063.
2
Functional analysis of dynactin and cytoplasmic dynein in slow axonal transport.动力蛋白激活蛋白和胞质动力蛋白在轴突慢速运输中的功能分析
J Neurosci. 1996 Nov 1;16(21):6742-52. doi: 10.1523/JNEUROSCI.16-21-06742.1996.
3
Ordered recruitment of dynactin to the microtubule plus-end is required for efficient initiation of retrograde axonal transport.动力蛋白激活蛋白复合物向微管正极的定向募集对于逆行轴突运输的有效起始是必需的。
J Neurosci. 2013 Aug 7;33(32):13190-203. doi: 10.1523/JNEUROSCI.0935-13.2013.
4
Ankyrin-B interactions with spectrin and dynactin-4 are required for dystrophin-based protection of skeletal muscle from exercise injury.锚蛋白-B 与血影蛋白和动力蛋白-4 的相互作用对于肌营养不良蛋白保护骨骼肌免受运动损伤是必需的。
J Biol Chem. 2011 Mar 4;286(9):7370-8. doi: 10.1074/jbc.M110.187831. Epub 2010 Dec 25.
5
βII-spectrin promotes mouse brain connectivity through stabilizing axonal plasma membranes and enabling axonal organelle transport.βII- spectrin 通过稳定轴突质膜和促进轴突细胞器运输来促进小鼠大脑连接。
Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15686-15695. doi: 10.1073/pnas.1820649116. Epub 2019 Jun 17.
6
Dynactin-dependent, dynein-driven vesicle transport in the absence of membrane proteins: a role for spectrin and acidic phospholipids.在缺乏膜蛋白的情况下，动力蛋白激活蛋白依赖、动力蛋白驱动的囊泡运输：血影蛋白和酸性磷脂的作用
Mol Cell. 2001 Jan;7(1):173-83. doi: 10.1016/s1097-2765(01)00165-4.
7
Ankyrin-B is a PI3P effector that promotes polarized α5β1-integrin recycling via recruiting RabGAP1L to early endosomes.锚蛋白B是一种PI3P效应蛋白，它通过将RabGAP1L招募到早期内体来促进极化的α5β1整合素循环利用。
Elife. 2016 Oct 8;5:e20417. doi: 10.7554/eLife.20417.
8
Regulation of dynein-dynactin-driven vesicular transport.动力蛋白-动力蛋白激活蛋白驱动的囊泡运输的调控
Traffic. 2017 Jun;18(6):336-347. doi: 10.1111/tra.12475. Epub 2017 Mar 28.
9
Dynactin regulates bidirectional transport of dense-core vesicles in the axon and dendrites of cultured hippocampal neurons.动力蛋白激活蛋白调节培养海马神经元轴突和树突中致密核心囊泡的双向运输。
Neuroscience. 2009 Sep 15;162(4):1001-10. doi: 10.1016/j.neuroscience.2009.05.038. Epub 2009 Jun 2.
10
Disruption of the dynein-dynactin complex unveils motor-specific functions in osteoclast formation and bone resorption.动力蛋白-动力蛋白激活蛋白复合物的破坏揭示了其在破骨细胞形成和骨吸收中的运动特异性功能。
J Bone Miner Res. 2013 Jan;28(1):119-34. doi: 10.1002/jbmr.1725.

引用本文的文献

1
Ankyrin-B modulates mitochondrial fission in skeletal muscle and is required for optimal endurance exercise capacity.锚蛋白B调节骨骼肌中的线粒体分裂，是最佳耐力运动能力所必需的。
Nat Commun. 2025 Aug 25;16(1):7671. doi: 10.1038/s41467-025-62977-3.
2
Regulation of neuronal ankyrin localization and function by post-translational modifications.翻译后修饰对神经元锚蛋白定位和功能的调控
Biochem Soc Trans. 2025 Apr 30;53(2):497-507. doi: 10.1042/BST20253016.
3
Fat traffic control: S-acylation in axonal transport.脂肪运输调控：轴突运输中的S-酰化作用

本文引用的文献

1
Spectrin- and ankyrin-based membrane domains and the evolution of vertebrates.基于 spectrin 和 ankyrin 的膜结构域与脊椎动物的演化。
Curr Top Membr. 2013;72:1-37. doi: 10.1016/B978-0-12-417027-8.00001-5.
2
Regulation of axon growth by the JIP1-AKT axis.JIP1-AKT 轴对轴突生长的调节。
J Cell Sci. 2014 Jan 1;127(Pt 1):230-9. doi: 10.1242/jcs.137208. Epub 2013 Nov 6.
3
Regulation of mammalian autophagy by class II and III PI 3-kinases through PI3P synthesis.通过 PI3P 合成调控哺乳动物自噬的 II 类和 III 类 PI3 激酶。
Mol Pharmacol. 2025 Jun;107(6):100039. doi: 10.1016/j.molpha.2025.100039. Epub 2025 Apr 16.
4
Ankyrins are dispensable for mechanotransduction by cochlear hair cells.锚蛋白对于耳蜗毛细胞的机械转导并非必需。
Hear Res. 2025 Apr;459:109224. doi: 10.1016/j.heares.2025.109224. Epub 2025 Mar 1.
5
Axon initial segment structure and function in health and disease.轴突起始段在健康与疾病中的结构和功能。
Physiol Rev. 2025 Apr 1;105(2):765-801. doi: 10.1152/physrev.00030.2024. Epub 2024 Oct 31.
6
Cargo specificity, regulation, and therapeutic potential of cytoplasmic dynein.细胞质动力蛋白的货物特异性、调节及治疗潜力。
Exp Mol Med. 2024 Apr;56(4):827-835. doi: 10.1038/s12276-024-01200-7. Epub 2024 Apr 1.
7
Physical and functional convergence of the autism risk genes Scn2a and Ank2 in neocortical pyramidal cell dendrites.自闭症风险基因 Scn2a 和 Ank2 在新皮层锥体神经元树突中的物理和功能趋同。
Neuron. 2024 Apr 3;112(7):1133-1149.e6. doi: 10.1016/j.neuron.2024.01.003. Epub 2024 Jan 29.
8
HEATR5B associates with dynein-dynactin and promotes motility of AP1-bound endosomal membranes.HEATR5B 与动力蛋白-动力素复合物结合，并促进 AP1 结合的内体膜的运动。
EMBO J. 2023 Dec 1;42(23):e114473. doi: 10.15252/embj.2023114473. Epub 2023 Oct 24.
9
Early developmental deletion of forebrain Ank2 causes seizure-related phenotypes by reshaping the synaptic proteome.早期大脑前 Ank2 的缺失通过重塑突触蛋白组导致与癫痫相关的表型。
Cell Rep. 2023 Jul 25;42(7):112784. doi: 10.1016/j.celrep.2023.112784. Epub 2023 Jul 9.
10
Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice.ANK2 突变小鼠皮质过度兴奋和与少年癫痫相关死亡中的 Kv7/KCNQ 钾通道。
Nat Commun. 2023 Jun 15;14(1):3547. doi: 10.1038/s41467-023-39203-z.
PLoS One. 2013 Oct 3;8(10):e76405. doi: 10.1371/journal.pone.0076405. eCollection 2013.
4
JIP1 regulates the directionality of APP axonal transport by coordinating kinesin and dynein motors.JIP1 通过协调驱动蛋白和动力蛋白来调节 APP 轴突运输的方向。
J Cell Biol. 2013 Aug 5;202(3):495-508. doi: 10.1083/jcb.201302078. Epub 2013 Jul 29.
5
Phosphatidylinositol 3-phosphate, a lipid that regulates membrane dynamics, protein sorting and cell signalling.磷脂酰肌醇 3-磷酸，一种调节膜动态、蛋白质分选和细胞信号转导的脂质。
Bioessays. 2013 Oct;35(10):900-12. doi: 10.1002/bies.201300064. Epub 2013 Jul 24.
6
A single divergent exon inhibits ankyrin-B association with the plasma membrane.单一发散外显子抑制锚蛋白-B 与质膜的结合。
J Biol Chem. 2013 May 24;288(21):14769-79. doi: 10.1074/jbc.M113.465328. Epub 2013 Apr 8.
7
PtdIns(4)P regulates retromer-motor interaction to facilitate dynein-cargo dissociation at the trans-Golgi network.PtdIns(4)P 调节逆行运输蛋白-动力蛋白复合物的相互作用，促进反式高尔基体网络中动力蛋白-货物的解离。
Nat Cell Biol. 2013 Apr;15(4):417-29. doi: 10.1038/ncb2710. Epub 2013 Mar 24.
8
JNK-interacting protein 3 mediates the retrograde transport of activated c-Jun N-terminal kinase and lysosomes.JNK 相互作用蛋白 3 介导激活的 c-Jun N 端激酶和溶酶体的逆行运输。
PLoS Genet. 2013;9(2):e1003303. doi: 10.1371/journal.pgen.1003303. Epub 2013 Feb 28.
9
TRAK/Milton motor-adaptor proteins steer mitochondrial trafficking to axons and dendrites.TRAK/Milton 运动适配器蛋白将线粒体运输导向轴突和树突。
Neuron. 2013 Feb 6;77(3):485-502. doi: 10.1016/j.neuron.2012.11.027.
10
Vesicular glycolysis provides on-board energy for fast axonal transport.囊泡糖解作用为快速轴突运输提供了车载能量。
Cell. 2013 Jan 31;152(3):479-91. doi: 10.1016/j.cell.2012.12.029.