The role of BMP/Smad signalling in motor neuron connectivity

BMP/Smad 信号在运动神经元连接中的作用

• 批准号: MR/J013331/1
• 负责人: Vasso Episkopou
• 金额: $ 92.53万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ013331%2F1
• 关键词: role; BMP; Smad; signalling; motor

Humans have billions of neurons that are all interconnected via axons and synapses. These provide neurons with the ability to communicate information over long distances. Wiring patterns are essential for body functions, movement, coordination cognition, learning and memory. How neurons grow their axons over great distances to reach and connect to other axons from different neurons or to muscles is not well understood. Axon elongation is one of the essential properties in neuronal connectivity and it is believed that in the adult it provides neurons with the ability to remodel their connections. This plasticity of neuronal connections underlies experience, learning and memory. Furthermore, neurons need to maintain some capacity to elongate their axons and regenerate their axonal projections to repair possible damage during life. Little is known about factors that regulate axon elongation particularly that of motor neurons, which possess the longest axons in the body i.e. from the spinal column to the end of the fingertips and toes. Understanding how our nervous system is wired will give us insights into how it develops and functions. Once we master this we can manipulate various aspects of connectivity to correct defects and disabilities or repair damaged neurons and cure neurodegenerative disease. In this research we aim to examine the role of the Bone Morphogenetic Protein factors in motor neuron connectivity in mouse models and provide basic information that would be beneficial for Motor Neuron disease and for peripheral axon regeneration.

人类有数十亿个神经元，它们都通过轴突和突触相互连接。这些为神经元提供了长距离传递信息的能力。布线模式对于身体功能、运动、协调认知、学习和记忆是必不可少的。神经元是如何长出轴突来到达并连接到来自不同神经元的其他轴突或肌肉的，这一点还没有得到很好的理解。轴突伸长是神经元连接的基本特性之一，并且据信在成人中它为神经元提供重塑其连接的能力。神经元连接的这种可塑性是经验、学习和记忆的基础。此外，神经元需要保持一定的能力来延长其轴突并再生其轴突投射以修复生命中可能的损伤。对调节轴突伸长的因素知之甚少，特别是运动神经元的轴突伸长，运动神经元拥有体内最长的轴突，即从脊柱到指尖和脚趾的末端。了解我们的神经系统是如何连接的将使我们深入了解它如何发展和运作。一旦我们掌握了这一点，我们就可以操纵连接的各个方面，以纠正缺陷和残疾，或修复受损的神经元，治愈神经退行性疾病。在这项研究中，我们的目的是研究骨形态发生蛋白因子在小鼠模型中运动神经元连接中的作用，并提供有利于运动神经元疾病和外周轴突再生的基本信息。

项目成果

Impact of a Single Nucleotide Polymorphism on the 3D Protein Structure and Ubiquitination Activity of E3 Ubiquitin Ligase Arkadia.

• DOI: 10.3389/fmolb.2022.844129
• 发表时间: 2022
• 期刊: Frontiers in molecular biosciences
• 影响因子: 5
• 作者: Birkou M;Raptis V;Marousis KD;Tsevis A;Bourikas K;Bentrop D;Episkopou V;Spyroulias GA
• 通讯作者: Spyroulias GA

NMR-based insights into the conformational and interaction properties of Arkadia RING-H2 E3 Ub ligase

• DOI: 10.1002/prot.24048
• 发表时间: 2012-03-01
• 期刊: PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
• 影响因子: 2.9
• 作者: Chasapis, Christos T.;Kandias, Nikolaos G.;Spyroulias, Georgios A.
• 通讯作者: Spyroulias, Georgios A.

E2 Partner Tunes the Ubiquitylation Specificity of Arkadia E3 Ubiquitin Ligase.

• DOI: 10.3390/cancers15041040
• 发表时间: 2023-02-07
• 期刊: Cancers
• 影响因子: 5.2

Rnf165/Ark2C enhances BMP-Smad signaling to mediate motor axon extension.

• DOI: 10.1371/journal.pbio.1001538
• 发表时间: 2013
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Kelly CE;Thymiakou E;Dixon JE;Tanaka S;Godwin J;Episkopou V
• 通讯作者: Episkopou V

Unveiling the Essential Role of Arkadia's Non-RING Elements in the Ubiquitination Process.

• DOI: 10.3390/ijms231810585
• 发表时间: 2022-09-13
• 期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• 影响因子: 5.6
• 作者: Birkou, Maria;Delegkou, Georgia N.;Marousis, Konstantinos D.;Fragkaki, Nefeli;Toro, Tamara;Episkopou, Vasso;Spyroulias, Georgios A.
• 通讯作者: Spyroulias, Georgios A.