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Functional characterization of a novel basal body/centrosomal protein

新型基底体/中心体蛋白的功能表征

基本信息

批准号：
218553926
负责人：
Professor Dr. Achim Gossler
金额：
--
依托单位：
Institut für Molekularbiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2014-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/218553926?language=en
关键词：
Functional characterization novel basal body

项目摘要

Cilia are dynamic cellular projections formed by stereotypically arranged microtubules that originate at a cortically located basal body, a centriolar structure that acts as a microtubule organizing center. Cilia have essential functions and defects in cilia or basal body formation, structure and function disrupt normal development and tissue homeostasis, and underlie various human diseases that are collectively referred to as ciliopathies. Likewise, abnormal centrosome biogenesis can lead to amplification of centrioles and supernumerary centrosomes, which in turn can lead to multipolar spindles, chromosome misseggregation and aneuploidy. We have identified the homeobox transcription factor NOTO as a pivotal regulator of ciliogenesis in early mouse embryos. Genes regulated by NOTO encode cilia components with known functions as well as proteins with unknown function that are present in the known ciliary proteome. Thus, genes regulated by NOTO are good candidates for novel components important for cilia/basal body formation and function. One of these genes referred to as M57 codes for a novel basal body/ centrosomal protein. Knock-down of M57 causes over-duplication of centrosomes suggesting that M57 is involved in the regulation of centriole biogenesis. We propose to comprehensively study M57 with respect to its biochemical, cellular and physiological functions to understand its mechanism of function and significance in the centrosome cycle.

纤毛是由起源于位于皮质的基体（中心粒结构，作为微管组织中心）的规则排列的微管形成的动态细胞突起。纤毛在纤毛或基体形成中具有基本功能和缺陷，结构和功能破坏正常发育和组织稳态，并且是统称为纤毛病的各种人类疾病的基础。同样地，异常的中心体生物发生可导致中心粒和额外中心体的扩增，这反过来又可导致多极纺锤体、染色体错误分段和非整倍体。我们已经确定了同源框转录因子诺托作为一个关键的调节纤毛发生在早期小鼠胚胎。由诺托调控的基因编码具有已知功能的纤毛组分以及存在于已知纤毛蛋白质组中的具有未知功能的蛋白质。因此，由诺托调控的基因是纤毛/基体形成和功能重要的新组分的良好候选物。这些基因之一称为M57编码一种新的基体/中心体蛋白。敲除M57导致中心体过度复制，表明M57参与了中心粒生物发生的调节。我们建议从生物化学、细胞学和生理学方面对M57进行全面研究，以了解其在中心体周期中的作用机制和意义。