Molecular Architecture of the Centriole Proteome: The Conserved WD40 Domain Protein POC1 Is Required for Centriole Duplication and Length Control
Molecular Architecture of the Centriole Proteome: The Conserved WD40 Domain Protein POC1 Is Required for Centriole Duplication and Length Control
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DOI：
10.1091/mbc.e08-06-0619
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发表时间：
2009-02-01
影响因子：
3.3
通讯作者：
Marshall, Wallace F.
中科院分区：
文献类型：
--
作者：
Keller, Lani C.;Geimer, Stefan;Marshall, Wallace F.
中心粒是由三重微管组成的有趣的圆柱形细胞器。蛋白质组学数据表明，除了微管蛋白之外，大量的蛋白质是中心粒复杂结构的形成和维持所必需的。从绿色衣藻中扩增预先存在的中心粒蛋白质组揭示了其他人类疾病基因，强调了中心粒在正常人体组织稳态中的重要性。我们发现两类睫状体疾病基因在基体蛋白质组中高度代表：囊性肾病（特别是肾单位营养不良）综合征，包括Meckel/Joubert样综合征和口-面-指综合征，由CEP 290，MKS 1，OFD 1和AHI 1/Jouberin蛋白质突变引起，以及锥-杆营养不良综合征基因，包括NPH-119/HRG 4，NPHP 4和RPGR 1。我们进一步表征了中心粒（POC）1的蛋白质组，该中心粒是一种高度丰富的含有WD 40结构域的中心粒蛋白。我们发现，POC 1被招募到新生的原中心粒和本地化在一个高度不对称的模式在成熟的中心粒对应的网站的基体纤维附件。在人类细胞中，POC 1的敲低导致中心粒复制减少，而过表达导致细长的中心粒样结构的出现。总之，这些数据表明，POC 1参与中心粒复制的早期步骤以及中心粒长度控制的后期步骤。
Centrioles are intriguing cylindrical organelles composed of triplet microtubules. Proteomic data suggest that a large number of proteins besides tubulin are necessary for the formation and maintenance of a centriole's complex structure. Expansion of the preexisting centriole proteome from the green alga Chlamydomonas reinhardtii revealed additional human disease genes, emphasizing the significance of centrioles in normal human tissue homeostasis. We found that two classes of ciliary disease genes were highly represented among the basal body proteome: cystic kidney disease (especially nephronophthisis) syndromes, including Meckel/Joubert-like and oral-facial-digital syndrome, caused by mutations in CEP290, MKS1, OFD1, and AHI1/Jouberin proteins and cone-rod dystrophy syndrome genes, including UNC-119/HRG4, NPHP4, and RPGR1. We further characterized proteome of the centriole (POC) 1, a highly abundant WD40 domaincontaining centriole protein. We found that POC1 is recruited to nascent procentrioles and localizes in a highly asymmetrical pattern in mature centrioles corresponding to sites of basal-body fiber attachment. Knockdown of POC1 in human cells caused a reduction in centriole duplication, whereas overexpression caused the appearance of elongated centriole-like structures. Together, these data suggest that POC1 is involved in early steps of centriole duplication as well as in the later steps of centriole length control.