• 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

PP2A-B55alpha 通过去磷酸化桥粒芯糖蛋白 C 末端来控制角质形成细胞黏附。

PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus.

机构信息

Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave., Chicago, IL, 60611, USA.

Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

出版信息

Sci Rep. 2023 Aug 5;13(1):12720. doi: 10.1038/s41598-023-37874-8.

DOI:10.1038/s41598-023-37874-8
PMID:37543698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10404246/
Abstract

Critical for the maintenance of epidermal integrity and function are attachments between intermediate filaments (IF) and intercellular junctions called desmosomes. The desmosomal cytoplasmic plaque protein desmoplakin (DP) is essential for anchoring IF to the junction. DP-IF interactions are regulated by a phospho-regulatory motif within the DP C-terminus controlling keratinocyte intercellular adhesion. Here we identify the protein phosphatase 2A (PP2A)-B55α holoenzyme as the major serine/threonine phosphatase regulating DP's C-terminus and consequent intercellular adhesion. Using a combination of chemical and genetic approaches, we show that the PP2A-B55α holoenzyme interacts with DP at intercellular membranes in 2D- and 3D- epidermal models and human skin samples. Our experiments demonstrate that PP2A-B55α regulates the phosphorylation status of junctional DP and is required for maintaining strong desmosome-mediated intercellular adhesion. These data identify PP2A-B55α as part of a regulatory module capable of tuning intercellular adhesion strength and a candidate disease target in desmosome-related disorders of the skin and heart.

摘要

表皮完整性和功能的维持关键在于细胞间连接的中间丝（IF）和细胞连接，这些连接被称为桥粒。桥粒细胞质斑块蛋白桥粒斑蛋白（DP）对于将 IF 锚定到连接点至关重要。DP-IF 相互作用受到 DP C 端磷酸化调节基序的调节，该基序控制角质形成细胞的细胞间黏附。在这里，我们确定蛋白磷酸酶 2A（PP2A）-B55α 全酶是调节 DP C 端及其随后的细胞间黏附的主要丝氨酸/苏氨酸磷酸酶。我们使用化学和遗传方法的组合表明，PP2A-B55α 全酶在 2D 和 3D 表皮模型和人皮肤样本中的细胞间膜上与 DP 相互作用。我们的实验表明，PP2A-B55α 调节连接 DP 的磷酸化状态，并且对于维持强桥粒介导的细胞间黏附是必需的。这些数据表明，PP2A-B55α 是能够调节细胞间黏附强度的调节模块的一部分，并且是皮肤和心脏桥粒相关疾病的候选疾病靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/75e6a4350cf8/41598_2023_37874_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/539632b7cf3e/41598_2023_37874_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/dcad6debc69a/41598_2023_37874_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/a993297f6cbe/41598_2023_37874_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/7d11587a1a42/41598_2023_37874_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/75e6a4350cf8/41598_2023_37874_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/539632b7cf3e/41598_2023_37874_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/dcad6debc69a/41598_2023_37874_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/a993297f6cbe/41598_2023_37874_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/7d11587a1a42/41598_2023_37874_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae08/10404246/75e6a4350cf8/41598_2023_37874_Fig5_HTML.jpg

相似文献

1
PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus.PP2A-B55alpha 通过去磷酸化桥粒芯糖蛋白 C 末端来控制角质形成细胞黏附。
Sci Rep. 2023 Aug 5;13(1):12720. doi: 10.1038/s41598-023-37874-8.
2
Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival by the B55alpha regulatory subunit targeting of the protein phosphatase 2A holoenzyme to Akt.通过将蛋白磷酸酶2A全酶的B55α调节亚基靶向Akt来调节Akt的苏氨酸-308磷酸化、细胞增殖和存活。
J Biol Chem. 2008 Jan 25;283(4):1882-92. doi: 10.1074/jbc.M709585200. Epub 2007 Nov 27.
3
Breaking the connection: displacement of the desmosomal plaque protein desmoplakin from cell-cell interfaces disrupts anchorage of intermediate filament bundles and alters intercellular junction assembly.切断连接：桥粒斑蛋白桥粒芯蛋白从细胞-细胞界面的位移破坏了中间丝束的锚定并改变了细胞间连接组装。
J Cell Biol. 1996 Aug;134(4):985-1001. doi: 10.1083/jcb.134.4.985.
4
PP2A/B55α substrate recruitment as defined by the retinoblastoma-related protein p107.PP2A/B55α 底物募集由视网膜母细胞瘤相关蛋白 p107 定义。
Elife. 2021 Oct 18;10:e63181. doi: 10.7554/eLife.63181.
5
Clustering of desmosomal cadherins by desmoplakin is essential for cell-cell adhesion.桥粒钙黏蛋白通过桥粒斑蛋白的聚集对于细胞-细胞黏附是必需的。
Acta Physiol (Oxf). 2021 Apr;231(4):e13609. doi: 10.1111/apha.13609. Epub 2021 Jan 19.
6
Protein phosphatase 2A-mediated flotillin-1 dephosphorylation up-regulates endothelial cell migration and angiogenesis regulation.蛋白磷酸酶 2A 介导的 flotillin-1 去磷酸化上调内皮细胞迁移和血管生成调节。
J Biol Chem. 2019 Dec 27;294(52):20196-20206. doi: 10.1074/jbc.RA119.007980. Epub 2019 Nov 21.
7
Activation of p107 by fibroblast growth factor, which is essential for chondrocyte cell cycle exit, is mediated by the protein phosphatase 2A/B55α holoenzyme.成纤维细胞生长因子通过蛋白磷酸酶 2A/B55α 全酶激活 p107，这对于软骨细胞细胞周期退出是必不可少的。
Mol Cell Biol. 2013 Aug;33(16):3330-42. doi: 10.1128/MCB.00082-13. Epub 2013 Jun 17.
8
Increased keratinocyte proliferation initiated through downregulation of desmoplakin by RNA interference.通过RNA干扰下调桥粒斑蛋白引发角质形成细胞增殖增加。
Exp Cell Res. 2007 Jul 1;313(11):2336-44. doi: 10.1016/j.yexcr.2007.01.010. Epub 2007 Jan 30.
9
Dephosphorylation of the HIV-1 restriction factor SAMHD1 is mediated by PP2A-B55α holoenzymes during mitotic exit.HIV-1 限制因子 SAMHD1 的去磷酸化是由有丝分裂退出期间的 PP2A-B55α 全酶介导的。
Nat Commun. 2018 Jun 8;9(1):2227. doi: 10.1038/s41467-018-04671-1.
10
The B55α regulatory subunit of protein phosphatase 2A mediates fibroblast growth factor-induced p107 dephosphorylation and growth arrest in chondrocytes.蛋白磷酸酶 2A 的 B55α 调节亚基介导成纤维细胞生长因子诱导的软骨细胞中 p107 的去磷酸化和生长阻滞。
Mol Cell Biol. 2013 Aug;33(15):2865-78. doi: 10.1128/MCB.01730-12. Epub 2013 May 28.

引用本文的文献

1
Desmoplakin tail domain position in the desmosomal plaque is isoform dependent.桥粒斑蛋白尾部结构域在桥粒斑中的位置取决于同工型。
bioRxiv. 2025 Feb 3:2025.02.03.636241. doi: 10.1101/2025.02.03.636241.
2
Desmosomes at a glance.桥粒概述。
J Cell Sci. 2024 Jun 15;137(12). doi: 10.1242/jcs.261899. Epub 2024 Jun 28.
3
DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5.DPM1 通过 SERPINB5 调节桥粒黏附和表皮分化。

本文引用的文献

1
PP2A-B55: substrates and regulators in the control of cellular functions.PP2A-B55：控制细胞功能的底物和调节剂。
Oncogene. 2022 Jan;41(1):1-14. doi: 10.1038/s41388-021-02068-x. Epub 2021 Oct 22.
2
Dynamic loading of human engineered heart tissue enhances contractile function and drives a desmosome-linked disease phenotype.动态加载人类工程心脏组织可增强收缩功能并引发桥粒连接疾病表型。
Sci Transl Med. 2021 Jul 21;13(603). doi: 10.1126/scitranslmed.abd1817.
3
Desmosomes polarize and integrate chemical and mechanical signaling to govern epidermal tissue form and function.
J Cell Biol. 2024 Apr 1;223(4). doi: 10.1083/jcb.202305006. Epub 2024 Mar 13.
桥粒将化学信号和机械信号极化并整合，以调控表皮组织的形态和功能。
Curr Biol. 2021 Aug 9;31(15):3275-3291.e5. doi: 10.1016/j.cub.2021.05.021. Epub 2021 Jun 8.
4
Hair and skin predict cardiomyopathies: Carvajal and erythrokeratodermia cardiomyopathy syndromes.毛发和皮肤表现可预测心肌病：卡瓦哈尔综合征和红皮病性心肌病综合征。
Pediatr Dermatol. 2021 Jan;38(1):31-38. doi: 10.1111/pde.14478. Epub 2020 Dec 4.
5
Proximity Ligation Assay for Detecting Protein-Protein Interactions and Protein Modifications in Cells and Tissues in Situ.原位检测细胞和组织中蛋白质-蛋白质相互作用和蛋白质修饰的邻近连接分析。
Curr Protoc Cell Biol. 2020 Dec;89(1):e115. doi: 10.1002/cpcb.115.
6
Mechanics of a multilayer epithelium instruct tumour architecture and function.多层上皮的力学特性可指导肿瘤的结构和功能。
Nature. 2020 Sep;585(7825):433-439. doi: 10.1038/s41586-020-2695-9. Epub 2020 Sep 2.
7
Knockout Mice Reveal That Protein Phosphatase 2A Regulatory Subunit, PP2A-B55α, Is an Essential Regulator of Neuronal and Epidermal Embryonic Development.基因敲除小鼠研究表明，蛋白磷酸酶2A调节亚基PP2A - B55α是神经元和表皮胚胎发育的重要调节因子。
Front Cell Dev Biol. 2020 Jun 5;8:358. doi: 10.3389/fcell.2020.00358. eCollection 2020.
8
Protein exchange is reduced in calcium-independent epithelial junctions.钙非依赖性上皮连接中蛋白交换减少。
J Cell Biol. 2020 Jun 1;219(6). doi: 10.1083/jcb.201906153.
9
HYVIA™: A novel, topical chia seed extract that improves skin hydration.HYVIA™：一种新型的局部用奇亚籽提取物，可改善皮肤水合作用。
J Cosmet Dermatol. 2020 Sep;19(9):2386-2393. doi: 10.1111/jocd.13469. Epub 2020 May 27.
10
Scaling up single-cell mechanics to multicellular tissues - the role of the intermediate filament-desmosome network.单细胞力学向多细胞组织的扩展 - 中间丝-桥粒网络的作用。
J Cell Sci. 2020 Mar 16;133(6):jcs228031. doi: 10.1242/jcs.228031.