New signaling mechanisms in myelination

髓鞘形成的新信号机制

• 批准号: BB/N015142/1
• 负责人: Dingenus Meijer
• 金额: $ 77.44万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN015142%2F1
• 关键词: New; signaling; mechanisms; myelination

The development and function of the tissues in our body depend on the continued interaction between the cells that make up the tissue. Cells are continuously talking to each other through molecules they send out or display on their surface. Neighbouring cells need to be able to sense and respond to these signals, so they have receptors for them. The signals and receptors come in many different varieties, and understanding their function is key to understanding animal and plant development. In this work we will examine the role of a signal and receptor molecule that are important for the development and function of the insulating layer (called the myelin sheath) that surrounds many of the nerve cells. These nerves trigger our senses and steer our muscles and the myelin sheath is important for the fast relay of information along our nerves. Highly similar signalling and receptor molecules exist in other parts of the brain where they fulfil other important functions, but it is not known if they all act in a similar way. We aim to elucidate how these signal:receptor molecules work in myelin formation and compare it with what we know about related proteins in other parts of the brain. This will give us deeper insight into the way these molecules work and how disturbances of these signals lead to developmental defects and neurological disease.

我们体内组织的发育和功能取决于组成组织的细胞之间持续的相互作用。细胞通过它们发出或显示在其表面的分子不断地相互交流。邻近的细胞需要能够感知并对这些信号做出反应，所以它们有相应的受体。信号和受体有许多不同的种类，了解它们的功能是理解动植物发育的关键。在这项工作中，我们将研究信号和受体分子的作用，它们对包围许多神经细胞的绝缘层（称为髓鞘）的发育和功能很重要。这些神经触发我们的感官，控制我们的肌肉，髓鞘对于信息沿神经的快速传递很重要。高度相似的信号和受体分子存在于大脑的其他部分，在那里它们完成其他重要的功能，但不知道它们是否都以相似的方式起作用。我们的目标是阐明这些信号受体分子如何在髓磷脂形成中起作用，并将其与我们所知道的大脑其他部分的相关蛋白质进行比较。这将使我们更深入地了解这些分子的工作方式，以及这些信号的干扰如何导致发育缺陷和神经系统疾病。

项目成果

LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period.

• DOI: 10.1083/jcb.202211031
• 发表时间: 2023-04-03
• 期刊: The Journal of cell biology

STAT3 Controls the Long-Term Survival and Phenotype of Repair Schwann Cells during Nerve Regeneration.

• DOI: 10.1523/jneurosci.3481-16.2017
• 发表时间: 2017-04-19
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Benito C;Davis CM;Gomez-Sanchez JA;Turmaine M;Meijer D;Poli V;Mirsky R;Jessen KR
• 通讯作者: Jessen KR

A reverse genetics and genomics approach to gene paralog function and disease: Myokymia and the juxtaparanode.

研究基因旁系同源功能和疾病的反向遗传学和基因组学方法：肌颤搐和并列旁节。

• DOI: 10.1016/j.ajhg.2022.07.006
• 发表时间: 2022
• 期刊: American journal of human genetics
• 影响因子: 9.8
• 作者: Marafi,Dana;Kozar,Nina;Duan,Ruizhi;Bradley,Stephen;Yokochi,Kenji;AlMutairi,Fuad;Saadi,NebalWaill;Whalen,Sandra;Brunet,Theresa;Kotzaeridou,Urania;Choukair,Daniela;Keren,Boris;Nava,Caroline;Kato,Mitsuhiro;Arai,Hiroshi;Froukh,
• 通讯作者: Froukh,