权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The actin nucleator Cordon-Bleu (Cobl) - elucidation of regulatory mechanisms and cellular function - II

肌动蛋白成核剂 Cordon-Bleu (Cobl) - 阐明调节机制和细胞功能 - II

基本信息

批准号：
192290875
负责人：
Privatdozent Dr. Michael Manfred Kessels
金额：
--
依托单位：
Institut für Biochemie I
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2011
资助国家：
德国
起止时间：
2010-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/192290875?language=en
关键词：
actin nucleator Cordon Bleu Cobl

项目摘要

Actin filament polymerization is essential for processes as diverse as cell morphology control, the formation of multicellular networks, cell migration and membrane trafficking processes. Indispensable is thereby a tight spatial and temporal control of actin filament nucleation. With the multiple WH2 domain-containing protein Cobl, we have identified a novel and very powerful actin nucleator. Our studies have thereby unraveled that Cobl plays an important role in proper formation of neuronal cell morphology - a prerequisite for the formation of functional neuronal networks. Analyses on the tissue and organism level now aim at revealing the structural and functional pathophysiological consequences of an impaired neuromorphogenesis upon Cobl deficiency. The successful establishment of Cobl-deficient organisms has furthermore already allowed first insights into the role of this new actin nucleator in cellular development, differentiation and function in the intact organism. These studies show among other phenotypes strikingly that different types of ciliary structures rely on the function of the actin nucleator Cobl. Ciliopathies, genetically inherited defects of these sensory cell surface structures, span a wide range of pleiotropic clinical phenotypes including frequently neurodevelopmental defects. Subsequent investigations will address the underlying mechanisms and shall disclose the exact role of Cobl-mediated cortical actin dynamics in the establishment of ciliary structures and reveal the pathophysiological consequences of a Cobl-deficiency on ciliogenesis and neuronal development.The analysis of the consequences of a loss of Cobl at the cellular, tissue and organism level is expected to significantly expand our molecular understanding of the functions of the cortical actin cytoskeleton - functions that are indispensable for live of all higher eukaryots.

肌动蛋白丝聚合对于细胞形态控制、多细胞网络的形成、细胞迁移和膜运输过程等多种过程都是必不可少的。因此，抑制是肌动蛋白丝成核的严格的空间和时间控制。通过含有多个WH 2结构域的蛋白质Cobl，我们发现了一种新型且非常强大的肌动蛋白成核剂。因此，我们的研究揭示了Cobl在神经元细胞形态的正确形成中起着重要作用-这是功能性神经元网络形成的先决条件。对组织和生物体水平的分析现在旨在揭示Cobl缺陷后受损的神经形态发生的结构和功能病理生理学后果。此外，Cobl缺陷生物体的成功建立已经允许首次深入了解这种新的肌动蛋白成核剂在完整生物体中的细胞发育，分化和功能中的作用。这些研究在其他表型中引人注目地表明，不同类型的纤毛结构依赖于肌动蛋白成核剂Cobl的功能。纤毛病是这些感觉细胞表面结构的遗传性缺陷，跨越广泛的多效性临床表型，经常包括神经发育缺陷。随后的研究将解决潜在的机制，并将揭示Cobl介导的皮质肌动蛋白动力学在纤毛结构建立中的确切作用，并揭示Cobl缺乏对纤毛发生和神经元发育的病理生理学后果。组织和生物体水平有望显著扩展我们对皮层肌动蛋白细胞骨架功能的分子理解-这些功能对于所有高等真核生物的生命是不可或缺的。