Functional characterization of a novel basal body/centrosomal protein

纤毛是由典型排列的微管形成的动态细胞突起，这些微管起源于位于皮质位置的基底体，基体是作为微管组织中心的中心粒结构。纤毛在纤毛或基底体的形成中具有基本的功能和缺陷，结构和功能扰乱正常发育和组织动态平衡，是人类各种疾病的基础，统称为纤毛病。同样，中心体生物发生异常会导致中心粒和多余中心体的放大，进而导致多极纺锤体、染色体错聚和非整倍体。我们已经确定同源盒转录因子Noto是小鼠早期胚胎纤毛发生的关键调节因子。由NOTO调控的基因编码已知功能的纤毛成分以及已知纤毛蛋白质组中存在的未知功能的蛋白质。因此，受NOTO调控的基因是对纤毛/基底体形成和功能重要的新成分的很好候选者。其中一个被称为M57的基因编码一种新的基底体/中心体蛋白。M57的敲除导致中心体的过度复制，表明M57参与了中心粒生物发生的调节。我们建议从生化、细胞和生理功能方面对M57进行综合研究，以了解其在中心体周期中的作用机制和意义。

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.