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对耳石发育至关重要的蛋白质的表达、功能和结构分析。

Expression, functional, and structural analysis of proteins critical for otoconia development.

机构信息

Vestibular Neurogenetics Laboratory, Boys Town National Research Hospital, Omaha, Nebraska 68131, USA.

出版信息

Dev Dyn. 2010 Oct;239(10):2659-73. doi: 10.1002/dvdy.22405.

DOI:10.1002/dvdy.22405
PMID:20803598
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3064886/
Abstract

Otoconia, developed during late gestation and perinatal stages, couple mechanic force to the sensory hair cells in the vestibule for motion detection and bodily balance. In the present work, we have investigated whether compensatory deposition of another protein(s) may have taken place to partially alleviate the detrimental effects of Oc90 deletion by analyzing a comprehensive list of plausible candidates, and have found a drastic increase in the deposition of Sparc-like 1 (aka Sc1 or hevin) in Oc90 null versus wt otoconia. We show that such up-regulation is specific to Sc1, and that stable transfection of Oc90 and Sc1 full-length expression constructs in NIH/3T3 cells indeed promotes matrix calcification. Analysis and modeling of Oc90 and Sc1 protein structures show common features that may be critical requirements for the otoconial matrix backbone protein. Such information will serve as the foundation for future regenerative purposes.

摘要

耳石在胚胎后期和围产期发育,将机械力传递给前庭感觉毛细胞,以进行运动检测和身体平衡。在本工作中,我们通过分析一整套可能的候选蛋白,研究了是否发生了另一种(或多种)蛋白的代偿性沉积,以部分减轻 Oc90 缺失的有害影响,发现 Oc90 缺失的耳石中 Sparc 样 1(又名 Sc1 或 hevin)的沉积明显增加。我们表明这种上调是 Sc1 特有的,并且在 NIH/3T3 细胞中稳定转染 Oc90 和 Sc1 全长表达构建体确实促进了基质钙化。对 Oc90 和 Sc1 蛋白结构的分析和建模显示出共同的特征,这些特征可能是耳石基质骨干蛋白的关键要求。这些信息将为未来的再生目的提供基础。

相似文献

1
Expression, functional, and structural analysis of proteins critical for otoconia development.对耳石发育至关重要的蛋白质的表达、功能和结构分析。
Dev Dyn. 2010 Oct;239(10):2659-73. doi: 10.1002/dvdy.22405.
2
Matrix recruitment and calcium sequestration for spatial specific otoconia development.基质招募和钙螯合作用促进空间特异性耳石发育。
PLoS One. 2011;6(5):e20498. doi: 10.1371/journal.pone.0020498. Epub 2011 May 31.
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Functional cooperation between two otoconial proteins Oc90 and Nox3.两种耳石蛋白 Oc90 和 Nox3 之间的功能合作。
J Vestib Res. 2021;31(6):441-449. doi: 10.3233/VES-201591.
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Gene targeting reveals the role of Oc90 as the essential organizer of the otoconial organic matrix.基因靶向技术揭示了Oc90作为耳石有机基质关键组织者的作用。
Dev Biol. 2007 Apr 15;304(2):508-24. doi: 10.1016/j.ydbio.2007.01.013. Epub 2007 Jan 12.
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Otoconin-90 deletion leads to imbalance but normal hearing: a comparison with other otoconia mutants.耳石素-90缺失导致失衡但听力正常:与其他耳石突变体的比较。
Neuroscience. 2008 Apr 22;153(1):289-99. doi: 10.1016/j.neuroscience.2008.01.055. Epub 2008 Feb 10.
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Osteopontin is not critical for otoconia formation or balance function.骨桥蛋白对于耳石形成或平衡功能并非至关重要。
J Assoc Res Otolaryngol. 2008 Jun;9(2):191-201. doi: 10.1007/s10162-008-0117-z. Epub 2008 May 6.
7
SPARC-like 1 (SC1) is a diversely expressed and developmentally regulated matricellular protein that does not compensate for the absence of SPARC in the CNS.富含半胱氨酸酸性分泌蛋白(SPARC)样蛋白 1(SC1)是一种表达广泛且发育调控的细胞基质蛋白,它不能弥补中枢神经系统中 SPARC 的缺失。
J Comp Neurol. 2012 Aug 15;520(12):2575-90. doi: 10.1002/cne.23029.
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Otoc1: a novel otoconin-90 ortholog required for otolith mineralization in zebrafish.Otoc1:一种斑马鱼耳石矿化所需的新型耳钙蛋白-90直系同源物。
Dev Neurobiol. 2008 Feb 1;68(2):209-22. doi: 10.1002/dneu.20587.
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Mechanisms of otoconia and otolith development.耳石和耳石膜发育的机制。
Dev Dyn. 2015 Mar;244(3):239-53. doi: 10.1002/dvdy.24195. Epub 2014 Oct 18.
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In vitro effects of recombinant otoconin 90 upon calcite crystal growth. Significance of tertiary structure.重组耳石蛋白 90 对方解石晶体生长的体外影响。三级结构的意义。
Hear Res. 2010 Sep 1;268(1-2):172-83. doi: 10.1016/j.heares.2010.05.019. Epub 2010 Jun 2.

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本文引用的文献

1
Calbindin and S100 protein expression in the developing inner ear in mice.小鼠内耳发育过程中钙结合蛋白和S100蛋白的表达
J Comp Neurol. 2009 Apr 10;513(5):469-82. doi: 10.1002/cne.21967.
2
Sparc protein is required for normal growth of zebrafish otoliths.Sparc蛋白是斑马鱼耳石正常生长所必需的。
J Assoc Res Otolaryngol. 2008 Dec;9(4):436-51. doi: 10.1007/s10162-008-0137-8. Epub 2008 Sep 11.
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Mineral deposition in the extracellular matrices of vertebrate tissues: identification of possible apatite nucleation sites on type I collagen.
Biomolecules. 2022 Sep 9;12(9):1266. doi: 10.3390/biom12091266.
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Vitamin D Insufficiency/Deficiency in Patients with Recurrent Benign Paroxysmal Positional Vertigo.维生素 D 缺乏/不足与复发性良性阵发性位置性眩晕患者。
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Whole-Genome Sequencing and Genome-Wide Studies of Spiny Head Croaker () Reveals Potential Insights for Well-Developed Otoliths in the Family Sciaenidae.棘头黄姑鱼全基因组测序及全基因组研究揭示了对石首鱼科发达耳石的潜在见解。
Front Genet. 2021 Sep 30;12:730255. doi: 10.3389/fgene.2021.730255. eCollection 2021.
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Relation between vitamin D deficiency and benign paroxysmal positional vertigo.维生素 D 缺乏与良性阵发性位置性眩晕的关系。
Sci Rep. 2021 Aug 19;11(1):16855. doi: 10.1038/s41598-021-96445-x.
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Spatiotemporal dynamics of inner ear sensory and non-sensory cells revealed by single-cell transcriptomics.单细胞转录组学揭示内耳感觉和非感觉细胞的时空动态。
Cell Rep. 2021 Jul 13;36(2):109358. doi: 10.1016/j.celrep.2021.109358.
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Development and evolution of the vestibular apparatuses of the inner ear.内耳前庭器官的发育和演化。
J Anat. 2021 Oct;239(4):801-828. doi: 10.1111/joa.13459. Epub 2021 May 28.
9
Functional cooperation between two otoconial proteins Oc90 and Nox3.两种耳石蛋白 Oc90 和 Nox3 之间的功能合作。
J Vestib Res. 2021;31(6):441-449. doi: 10.3233/VES-201591.
10
Effect of Vitamin D Injection in Recurrent Benign Paroxysmal Positional Vertigo with Vitamin D Deficiency.维生素D注射对维生素D缺乏的复发性良性阵发性位置性眩晕的影响。
Int Arch Otorhinolaryngol. 2020 Oct;24(4):e423-e428. doi: 10.1055/s-0039-3402431. Epub 2020 Feb 7.
矿物质在脊椎动物组织细胞外基质中的沉积:I型胶原蛋白上可能的磷灰石成核位点的鉴定。
Cells Tissues Organs. 2009;189(1-4):20-4. doi: 10.1159/000151454. Epub 2008 Aug 15.
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SCPP gene evolution and the dental mineralization continuum.SCPP基因进化与牙齿矿化连续过程
J Dent Res. 2008 Jun;87(6):520-31. doi: 10.1177/154405910808700608.
5
Osteopontin is not critical for otoconia formation or balance function.骨桥蛋白对于耳石形成或平衡功能并非至关重要。
J Assoc Res Otolaryngol. 2008 Jun;9(2):191-201. doi: 10.1007/s10162-008-0117-z. Epub 2008 May 6.
6
Identification of a novel matrix protein contained in a protein aggregate associated with collagen in fish otoliths.鉴定一种与鱼耳石中胶原蛋白相关的蛋白质聚集体中含有的新型基质蛋白。
FEBS J. 2008 May;275(10):2512-23. doi: 10.1111/j.1742-4658.2008.06400.x. Epub 2008 Apr 10.
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Otoconin-90 deletion leads to imbalance but normal hearing: a comparison with other otoconia mutants.耳石素-90缺失导致失衡但听力正常:与其他耳石突变体的比较。
Neuroscience. 2008 Apr 22;153(1):289-99. doi: 10.1016/j.neuroscience.2008.01.055. Epub 2008 Feb 10.
8
Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer.小整合素结合配体N-连接糖蛋白(SIBLINGs):癌症中的多功能蛋白
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Otoc1: a novel otoconin-90 ortholog required for otolith mineralization in zebrafish.Otoc1:一种斑马鱼耳石矿化所需的新型耳钙蛋白-90直系同源物。
Dev Neurobiol. 2008 Feb 1;68(2):209-22. doi: 10.1002/dneu.20587.
10
Molecular simulation of protein adsorption and desorption on hydroxyapatite surfaces.蛋白质在羟基磷灰石表面吸附和解吸的分子模拟
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