• 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

极性蛋白Par3通过内吞衔接蛋白Numb调节淀粉样前体蛋白（APP）的运输和加工。

The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb.

作者信息

Sun Miao, Asghar Suwaiba Z, Zhang Huaye

机构信息

Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States.

Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States.

出版信息

Neurobiol Dis. 2016 Sep;93:1-11. doi: 10.1016/j.nbd.2016.03.022. Epub 2016 Apr 9.

DOI:10.1016/j.nbd.2016.03.022
PMID:27072891
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4930744/
Abstract

The processing of amyloid precursor protein (APP) into β-amyloid peptide (Aβ) is a key step in the pathogenesis of Alzheimer's disease (AD), and trafficking dysregulations of APP and its secretases contribute significantly to altered APP processing. Here we show that the cell polarity protein Par3 plays an important role in APP processing and trafficking. We found that the expression of full length Par3 is significantly decreased in AD patients. Overexpression of Par3 promotes non-amyloidogenic APP processing, while depletion of Par3 induces intracellular accumulation of Aβ. We further show that Par3 functions by regulating APP trafficking. Loss of Par3 decreases surface expression of APP by targeting APP to the late endosome/lysosome pathway. Finally, we show that the effects of Par3 are mediated through the endocytic adaptor protein Numb, and Par3 functions by interfering with the interaction between Numb and APP. Together, our studies show a novel role for Par3 in regulating APP processing and trafficking.

摘要

淀粉样前体蛋白（APP）加工成β-淀粉样肽（Aβ）是阿尔茨海默病（AD）发病机制中的关键步骤，APP及其分泌酶的运输失调对APP加工改变有显著影响。在此我们表明，细胞极性蛋白Par3在APP加工和运输中起重要作用。我们发现AD患者中全长Par3的表达显著降低。Par3的过表达促进非淀粉样生成性APP加工，而Par3的缺失诱导Aβ在细胞内积累。我们进一步表明Par3通过调节APP运输发挥作用。Par3的缺失通过将APP靶向晚期内体/溶酶体途径降低APP的表面表达。最后，我们表明Par3的作用是通过内吞衔接蛋白Numb介导的，并且Par3通过干扰Numb与APP之间的相互作用发挥作用。总之，我们的研究表明Par3在调节APP加工和运输中具有新作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/bc451030c8d4/nihms780828f11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/9c26d5bfb18d/nihms780828f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/b33dfe1c0717/nihms780828f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/3b32a4b2d103/nihms780828f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/6f68e665cfee/nihms780828f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/14389ee67632/nihms780828f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/437cb036bddc/nihms780828f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/0fe466bcdbf3/nihms780828f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/5895b79b32d1/nihms780828f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/1d7a12d7ea9e/nihms780828f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/73509427a03c/nihms780828f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/bc451030c8d4/nihms780828f11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/9c26d5bfb18d/nihms780828f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/b33dfe1c0717/nihms780828f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/3b32a4b2d103/nihms780828f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/6f68e665cfee/nihms780828f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/14389ee67632/nihms780828f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/437cb036bddc/nihms780828f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/0fe466bcdbf3/nihms780828f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/5895b79b32d1/nihms780828f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/1d7a12d7ea9e/nihms780828f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/73509427a03c/nihms780828f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c488/4930744/bc451030c8d4/nihms780828f11.jpg

相似文献

1
The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb.极性蛋白Par3通过内吞衔接蛋白Numb调节淀粉样前体蛋白（APP）的运输和加工。
Neurobiol Dis. 2016 Sep;93:1-11. doi: 10.1016/j.nbd.2016.03.022. Epub 2016 Apr 9.
2
LDLR-related protein 10 (LRP10) regulates amyloid precursor protein (APP) trafficking and processing: evidence for a role in Alzheimer's disease.载脂蛋白相关蛋白 10（LRP10）调节淀粉样前体蛋白（APP）的运输和加工：在阿尔茨海默病中的作用证据。
Mol Neurodegener. 2012 Jun 26;7:31. doi: 10.1186/1750-1326-7-31.
3
CD2-associated protein (CD2AP) overexpression accelerates amyloid precursor protein (APP) transfer from early endosomes to the lysosomal degradation pathway.CD2 相关蛋白（CD2AP）过表达加速了淀粉样前体蛋白（APP）从早期内体向溶酶体降解途径的转移。
J Biol Chem. 2019 Jul 12;294(28):10886-10899. doi: 10.1074/jbc.RA118.005385. Epub 2019 May 28.
4
Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons.Par3 调控海马神经元中 APP 和 BACE1 的极化汇聚。
Neurobiol Aging. 2019 May;77:87-93. doi: 10.1016/j.neurobiolaging.2019.01.023. Epub 2019 Jan 30.
5
Amyloid precursor protein traffics from the Golgi directly to early endosomes in an Arl5b- and AP4-dependent pathway.淀粉样前体蛋白通过一种依赖于Arl5b和AP4的途径从高尔基体直接运输到早期内体。
Traffic. 2017 Mar;18(3):159-175. doi: 10.1111/tra.12465. Epub 2017 Jan 30.
6
Cellular Trafficking of Amyloid Precursor Protein in Amyloidogenesis Physiological and Pathological Significance.淀粉样前体蛋白在淀粉样生成中的细胞内转运：生理和病理意义。
Mol Neurobiol. 2019 Feb;56(2):812-830. doi: 10.1007/s12035-018-1106-9. Epub 2018 May 24.
7
Retention in endoplasmic reticulum 1 (RER1) modulates amyloid-β (Aβ) production by altering trafficking of γ-secretase and amyloid precursor protein (APP).内质网 1（RER1）的保留通过改变 γ-分泌酶和淀粉样前体蛋白（APP）的运输来调节淀粉样β（Aβ）的产生。
J Biol Chem. 2012 Nov 23;287(48):40629-40. doi: 10.1074/jbc.M112.418442. Epub 2012 Oct 5.
8
The Amyloid Precursor Protein is rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid.淀粉样前体蛋白从高尔基体迅速转运至溶酶体，并在那里被加工成β-淀粉样蛋白。
Mol Brain. 2014 Aug 1;7:54. doi: 10.1186/s13041-014-0054-1.
9
The physical approximation of APP and BACE-1: A key event in alzheimer's disease pathogenesis.淀粉样前体蛋白（APP）和 BACE-1 的物理近似：阿尔茨海默病发病机制中的关键事件。
Dev Neurobiol. 2018 Mar;78(3):340-347. doi: 10.1002/dneu.22556. Epub 2017 Nov 13.
10
Rab21, a Novel PS1 Interactor, Regulates γ-Secretase Activity via PS1 Subcellular Distribution.Rab21，一种新型的 PS1 相互作用蛋白，通过 PS1 的亚细胞分布调节 γ-分泌酶活性。
Mol Neurobiol. 2018 May;55(5):3841-3855. doi: 10.1007/s12035-017-0606-3. Epub 2017 May 25.

引用本文的文献

1
NUMB alternative splicing and isoform-specific functions in development and disease.NUMB在发育和疾病中的可变剪接及异构体特异性功能。
J Biol Chem. 2025 Mar;301(3):108215. doi: 10.1016/j.jbc.2025.108215. Epub 2025 Jan 23.
2
Effects of SPI1-mediated transcriptome remodeling on Alzheimer's disease-related phenotypes in mouse models of Aβ amyloidosis.SPI1 介导的转录组重构对 Aβ 淀粉样变性小鼠模型中阿尔茨海默病相关表型的影响。
Nat Commun. 2024 May 11;15(1):3996. doi: 10.1038/s41467-024-48484-x.
3
The Multitasker Protein: A Look at the Multiple Capabilities of NUMB.

本文引用的文献

1
MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism.MARK/Par1激酶通过依赖蛋白激酶A的机制在N-甲基-D-天冬氨酸受体下游被激活。
PLoS One. 2015 May 1;10(5):e0124816. doi: 10.1371/journal.pone.0124816. eCollection 2015.
2
The Amyloid Precursor Protein is rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid.淀粉样前体蛋白从高尔基体迅速转运至溶酶体，并在那里被加工成β-淀粉样蛋白。
Mol Brain. 2014 Aug 1;7:54. doi: 10.1186/s13041-014-0054-1.
3
Differential labeling of cell-surface and internalized proteins after antibody feeding of live cultured neurons.
多功能蛋白：探索 NUMB 的多种功能
Cells. 2023 Jan 15;12(2):333. doi: 10.3390/cells12020333.
4
CAV2 Regulates Mir-4723/Wnt7A Signalling Axis through Endocytosis and Epithelial-Mesenchymal Transition to Promote Proliferation, Invasion, and Metastasis of Pancreatic Cancer Cells.CAV2通过内吞作用和上皮-间质转化调节Mir-4723/Wnt7A信号轴，以促进胰腺癌细胞的增殖、侵袭和转移。
J Cancer. 2022 Apr 4;13(7):2200-2212. doi: 10.7150/jca.69617. eCollection 2022.
5
Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels.全基因组关联研究的荟萃分析确定了循环总 tau 水平的特定种族相关关联。
Commun Biol. 2022 Apr 8;5(1):336. doi: 10.1038/s42003-022-03287-y.
6
A novel non‑selective atypical PKC agonist could protect neuronal cell line from Aβ‑oligomer induced toxicity by suppressing Aβ generation.一种新型非选择性非典型蛋白激酶 C 激动剂可通过抑制 Aβ 的生成来保护神经元细胞系免受 Aβ-寡聚物诱导的毒性。
Mol Med Rep. 2022 May;25(5). doi: 10.3892/mmr.2022.12669. Epub 2022 Mar 4.
7
Willin/FRMD6: A Multi-Functional Neuronal Protein Associated with Alzheimer's Disease.Willin/FRMD6：一种与阿尔茨海默病相关的多功能神经元蛋白。
Cells. 2021 Nov 4;10(11):3024. doi: 10.3390/cells10113024.
8
Par3 cooperates with Sanpodo for the assembly of Notch clusters following asymmetric division of sensory organ precursor cells.Par3 与 Sanpodo 合作，在感觉器官前体细胞不对称分裂后组装 Notch 簇。
Elife. 2021 Oct 1;10:e66659. doi: 10.7554/eLife.66659.
9
Enhancing α-secretase Processing for Alzheimer's Disease-A View on SFRP1.增强α-分泌酶加工以治疗阿尔茨海默病——关于分泌型卷曲相关蛋白1的观点
Brain Sci. 2020 Feb 22;10(2):122. doi: 10.3390/brainsci10020122.
10
CD82-TRPM7-Numb signaling mediates age-related cognitive impairment.CD82-TRPM7-Numb 信号转导介导与年龄相关的认知障碍。
Geroscience. 2020 Apr;42(2):595-611. doi: 10.1007/s11357-020-00166-4. Epub 2020 Feb 22.
活培养神经元抗体孵育后细胞表面蛋白和内化蛋白的差异标记
J Vis Exp. 2014 Feb 12(84):e51139. doi: 10.3791/51139.
4
RalA promotes a direct exocyst-Par6 interaction to regulate polarity in neuronal development.RalA 促进外核蛋白-Par6 的直接相互作用，从而调节神经元发育中的极性。
J Cell Sci. 2014 Feb 1;127(Pt 3):686-99. doi: 10.1242/jcs.145037. Epub 2013 Nov 27.
5
Aβ secretion and plaque formation depend on autophagy.β淀粉样蛋白分泌和斑块形成依赖于自噬。
Cell Rep. 2013 Oct 17;5(1):61-9. doi: 10.1016/j.celrep.2013.08.042. Epub 2013 Oct 3.
6
The adhesion-GPCR BAI1 regulates synaptogenesis by controlling the recruitment of the Par3/Tiam1 polarity complex to synaptic sites.黏附 GPCR BAI1 通过控制 Par3/Tiam1 极性复合物向突触位点的募集来调节突触发生。
J Neurosci. 2013 Apr 17;33(16):6964-78. doi: 10.1523/JNEUROSCI.3978-12.2013.
7
The ageing haematopoietic stem cell compartment.衰老的造血干细胞池。
Nat Rev Immunol. 2013 May;13(5):376-89. doi: 10.1038/nri3433. Epub 2013 Apr 15.
8
Regulation of microtubule stability and organization by mammalian Par3 in specifying neuronal polarity.哺乳动物 Par3 通过调节微管的稳定性和组织来特异性调节神经元极性。
Dev Cell. 2013 Jan 14;24(1):26-40. doi: 10.1016/j.devcel.2012.11.014. Epub 2012 Dec 27.
9
Loss of Par3 promotes breast cancer metastasis by compromising cell-cell cohesion.缺失 Par3 通过损害细胞间黏附促进乳腺癌转移。
Nat Cell Biol. 2013 Feb;15(2):189-200. doi: 10.1038/ncb2663. Epub 2012 Dec 23.
10
Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis.缺失 Par3 极性蛋白可促进乳腺癌发生和转移。
Cancer Cell. 2012 Nov 13;22(5):601-14. doi: 10.1016/j.ccr.2012.10.003.