• 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

SH3KBP1通过内质网/肌浆网结构完整性促进骨骼肌纤维的形成和功能。

SH3KBP1 promotes skeletal myofiber formation and functionality through ER/SR architecture integrity.

作者信息

Guiraud Alexandre, Couturier Nathalie, Christin Emilie, Castellano Léa, Daura Marine, Kretz-Remy Carole, Janin Alexandre, Ghasemizadeh Alireza, Del Carmine Peggy, Monteiro Laloe, Rotard Ludivine, Sanchez Colline, Jacquemond Vincent, Burny Claire, Janczarski Stéphane, Durieux Anne-Cécile, Arnould David, Romero Norma Beatriz, Bui Mai Thao, Buchman Vladimir L, Julien Laura, Bitoun Marc, Gache Vincent

机构信息

CNRS/UCBL1 UMR 5261 - INSERM U1315, U1217, INMG-PGNM, INSERM, CNRS, Claude Bernard University Lyon 1, Lyon, France.

Laboratoire de Biologie et Modélisation de la Cellule, ENS de Lyon, Lyon, CEDEX 07, France.

出版信息

EMBO Rep. 2025 Apr;26(8):2166-2191. doi: 10.1038/s44319-025-00413-9. Epub 2025 Mar 10.

DOI:10.1038/s44319-025-00413-9
PMID:40065183
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12019163/
Abstract

Dynamic changes in the arrangement of myonuclei and the organization of the sarcoplasmic reticulum are important determinants of myofiber formation and muscle function. To find factors associated with muscle integrity, we perform an siRNA screen and identify SH3KBP1 as a new factor controlling myoblast fusion, myonuclear positioning, and myotube elongation. We find that the N-terminus of SH3KBP1 binds to dynamin-2 while the C-terminus associates with the endoplasmic reticulum through calnexin, which in turn control myonuclei dynamics and ER integrity, respectively. Additionally, in mature muscle fibers, SH3KBP1 contributes to the formation of triads and modulates the Excitation-Contraction Coupling process efficiency. In Dnm2 mice, a model for centronuclear myopathy (CNM), depletion of Sh3kbp1 expression aggravates CNM-related atrophic phenotypes and impaired autophagic flux in mutant skeletal muscle fiber. Altogether, our results identify SH3KBP1 as a new regulator of myofiber integrity and function.

摘要

肌细胞核排列的动态变化和肌浆网的组织是肌纤维形成和肌肉功能的重要决定因素。为了找到与肌肉完整性相关的因素，我们进行了一项小干扰RNA筛选，并确定SH3KBP1是控制成肌细胞融合、肌细胞核定位和肌管伸长的新因素。我们发现，SH3KBP1的N端与发动蛋白-2结合，而C端通过钙连蛋白与内质网结合，这反过来又分别控制肌细胞核动态和内质网完整性。此外，在成熟肌纤维中，SH3KBP1有助于三联体的形成，并调节兴奋-收缩偶联过程的效率。在中心核肌病（CNM）模型Dnm2小鼠中，Sh3kbp1表达的缺失会加重与CNM相关的萎缩表型，并损害突变型骨骼肌纤维中的自噬通量。总之，我们的结果确定SH3KBP1是肌纤维完整性和功能的新调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/da6e1192d3c5/44319_2025_413_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/b20c1ef05518/44319_2025_413_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/faf374645a01/44319_2025_413_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/6dcb6d5b072a/44319_2025_413_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/3f844c686193/44319_2025_413_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/466070af1e09/44319_2025_413_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/15133695e742/44319_2025_413_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/0c88d5e9359a/44319_2025_413_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/aef6e622699d/44319_2025_413_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/6651d8387a8b/44319_2025_413_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/5202a575ce50/44319_2025_413_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/9750ccbdb7d5/44319_2025_413_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/a1ef55eac09f/44319_2025_413_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/da6e1192d3c5/44319_2025_413_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/b20c1ef05518/44319_2025_413_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/faf374645a01/44319_2025_413_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/6dcb6d5b072a/44319_2025_413_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/3f844c686193/44319_2025_413_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/466070af1e09/44319_2025_413_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/15133695e742/44319_2025_413_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/0c88d5e9359a/44319_2025_413_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/aef6e622699d/44319_2025_413_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/6651d8387a8b/44319_2025_413_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/5202a575ce50/44319_2025_413_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/9750ccbdb7d5/44319_2025_413_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/a1ef55eac09f/44319_2025_413_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a41/12019163/da6e1192d3c5/44319_2025_413_Fig13_ESM.jpg

相似文献

1
SH3KBP1 promotes skeletal myofiber formation and functionality through ER/SR architecture integrity.SH3KBP1通过内质网/肌浆网结构完整性促进骨骼肌纤维的形成和功能。
EMBO Rep. 2025 Apr;26(8):2166-2191. doi: 10.1038/s44319-025-00413-9. Epub 2025 Mar 10.
2
Nuclear defects in skeletal muscle from a Dynamin 2-linked centronuclear myopathy mouse model.骨骼肌中的核缺陷源于与动力蛋白 2 相关的中心体核肌病的小鼠模型。
Sci Rep. 2019 Feb 7;9(1):1580. doi: 10.1038/s41598-018-38184-0.
3
Impaired excitation-contraction coupling in muscle fibres from the dynamin2 mouse model of centronuclear myopathy.动力蛋白 2 基因突变型中心核肌病肌纤维兴奋-收缩耦联障碍。
J Physiol. 2017 Dec 15;595(24):7369-7382. doi: 10.1113/JP274990. Epub 2017 Nov 21.
4
Dynamin-2 mutations linked to Centronuclear Myopathy impair actin-dependent trafficking in muscle cells.与中央核肌病相关的动力蛋白-2 突变会损害肌肉细胞中肌动蛋白依赖性运输。
Sci Rep. 2017 Jul 4;7(1):4580. doi: 10.1038/s41598-017-04418-w.
5
Centronuclear Myopathy Caused by Defective Membrane Remodelling of Dynamin 2 and BIN1 Variants.中心核肌病由 dynamin 2 和 BIN1 变异体的膜重塑缺陷引起。
Int J Mol Sci. 2022 Jun 3;23(11):6274. doi: 10.3390/ijms23116274.
6
Amphiphysin (BIN1) negatively regulates dynamin 2 for normal muscle maturation. amphiphysin (BIN1) 负调控动力蛋白 2 以促进正常肌肉成熟。
J Clin Invest. 2017 Dec 1;127(12):4477-4487. doi: 10.1172/JCI90542. Epub 2017 Nov 13.
7
Different in vivo impacts of dynamin 2 mutations implicated in Charcot-Marie-Tooth neuropathy or centronuclear myopathy.不同的活体内作用 动力蛋白 2 突变 牵涉到 腓骨肌萎缩症 或 中央核肌病。
Hum Mol Genet. 2019 Dec 15;28(24):4067-4077. doi: 10.1093/hmg/ddz249.
8
Mutant BIN1-Dynamin 2 complexes dysregulate membrane remodeling in the pathogenesis of centronuclear myopathy.突变 BIN1-动力蛋白 2 复合物在核性肌病发病机制中失调膜重塑。
J Biol Chem. 2021 Jan-Jun;296:100077. doi: 10.1074/jbc.RA120.015184. Epub 2020 Nov 21.
9
Mice with muscle-specific deletion of Bin1 recapitulate centronuclear myopathy and acute downregulation of dynamin 2 improves their phenotypes.肌特异性 Bin1 缺失的小鼠重现中心核肌病，并且动力蛋白 2 的急性下调改善了它们的表型。
Mol Ther. 2022 Feb 2;30(2):868-880. doi: 10.1016/j.ymthe.2021.08.006. Epub 2021 Aug 8.
10
Increased expression of wild-type or a centronuclear myopathy mutant of dynamin 2 in skeletal muscle of adult mice leads to structural defects and muscle weakness.在成年小鼠的骨骼肌中过度表达野生型或中心体肌病突变型 dynamin 2 会导致结构缺陷和肌肉无力。
Am J Pathol. 2011 May;178(5):2224-35. doi: 10.1016/j.ajpath.2011.01.054.

本文引用的文献

1
DNM2 levels normalization improves muscle phenotypes of a novel mouse model for moderate centronuclear myopathy.DNM2水平正常化改善了一种新型中度中央核性肌病小鼠模型的肌肉表型。
Mol Ther Nucleic Acids. 2023 Jul 17;33:321-334. doi: 10.1016/j.omtn.2023.07.003. eCollection 2023 Sep 12.
2
ER-phagy: selective autophagy of the endoplasmic reticulum.ER-phagy：内质网的选择性自噬。
EMBO Rep. 2022 Aug 3;23(8):e55192. doi: 10.15252/embr.202255192. Epub 2022 Jun 27.
3
Shielding of actin by the endoplasmic reticulum impacts nuclear positioning.
内质网对肌动蛋白的屏蔽作用影响核定位。
Nat Commun. 2022 May 19;13(1):2763. doi: 10.1038/s41467-022-30388-3.
4
The Sarcoplasmic Reticulum of Skeletal Muscle Cells: A Labyrinth of Membrane Contact Sites.骨骼肌细胞的肌浆网：膜接触位点的迷宫。
Biomolecules. 2022 Mar 23;12(4):488. doi: 10.3390/biom12040488.
5
Desmin interacts with STIM1 and coordinates Ca2+ signaling in skeletal muscle.结蛋白与 STIM1 相互作用并协调骨骼肌中的 Ca2+信号传导。
JCI Insight. 2021 Sep 8;6(17):e143472. doi: 10.1172/jci.insight.143472.
6
MACF1 controls skeletal muscle function through the microtubule-dependent localization of extra-synaptic myonuclei and mitochondria biogenesis.MACF1 通过微管依赖性的突触外肌细胞核和线粒体生物发生定位来控制骨骼肌功能。
Elife. 2021 Aug 27;10:e70490. doi: 10.7554/eLife.70490.
7
The Role of Autophagy in Skeletal Muscle Diseases.自噬在骨骼肌疾病中的作用。
Front Physiol. 2021 Mar 25;12:638983. doi: 10.3389/fphys.2021.638983. eCollection 2021.
8
Myonuclear content regulates cell size with similar scaling properties in mice and humans.肌核含量以相似的缩放特性调节小鼠和人类的细胞大小。
Nat Commun. 2020 Dec 8;11(1):6288. doi: 10.1038/s41467-020-20057-8.
9
Nuclear numbers in syncytial muscle fibers promote size but limit the development of larger myonuclear domains.合胞体肌纤维中的核数促进了肌纤维的大小，但限制了更大的肌核区域的发育。
Nat Commun. 2020 Dec 8;11(1):6287. doi: 10.1038/s41467-020-20058-7.
10
A location, location, location mutation impairs DNM2-mediated release of nascent autophagosomes from recycling endosomes.一个位置、位置、位置突变会损害 DNM2 介导的从再循环内体释放新生自噬体的过程。
Autophagy. 2020 Jul;16(7):1353-1354. doi: 10.1080/15548627.2020.1764210. Epub 2020 May 26.