期刊
EMBO JOURNAL
卷 30, 期 23, 页码 4790-4804出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2011.378
关键词
biogenesis; cell cycle; centrosome duplication; MCPH; microcephaly; procentriole formation
资金
- Academia Sinica
- National Science Council, ROC
Centriole duplication involves the growth of a procentriole next to the parental centriole. Mutations in STIL and CPAP/CENPJ cause primary microcephaly (MCPH). Here, we show that human STIL has an asymmetric localization to the daughter centriole and is required for procentriole formation. STIL levels oscillate during the cell cycle. Interestingly, STIL interacts directly with CPAP and forms a complex with hSAS6. A natural mutation of CPAP (E1235V) that causes MCPH in humans leads to significantly lower binding to STIL. Overexpression of STIL induced the formation of multiple procentrioles around the parental centriole. STIL depletion inhibited normal centriole duplication, Plk4-induced centriole amplification, and CPAP-induced centriole elongation, and resulted in a failure to localize hSAS6 and CPAP to the base of the nascent procentriole. Furthermore, hSAS6 depletion hindered STIL targeting to the procentriole, implying that STIL and hSAS6 are mutually dependent for their centriolar localization. Together, our results indicate that the two MCPH-associated proteins STIL and CPAP interact with each other and are required for procentriole formation, implying a central role of centriole biogenesis in MCPH. The EMBO Journal (2011) 30, 4790-4804. doi:10.1038/emboj.2011.378; Published online 21 October 2011
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