NEDD1-dependent recruitment of the gamma-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assembly.
NEDD1-dependent recruitment of the gamma-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assembly.
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DOI：
10.1083/jcb.200510028
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发表时间：
2006-02-13
影响因子：
7.8
通讯作者：
Merdes, Andreas
中科院分区：
文献类型：
--
作者：
Haren, Laurence;Remy, Marie-Helene;Bazin, Ingrid;Callebaut, Isabelle;Wright, Michel;Merdes, Andreas
中心体是体细胞中微管的主要组织结构。中心体微管成核依赖于γ-微管蛋白。在哺乳动物中，γ-微管蛋白与其他蛋白质结合形成一个大的复合物，即γ-微管蛋白环复合物（γTuRC）。我们表征了NEDD 1，一种与γTuRCs相关的中心体蛋白。我们发现，即使在NEDD 1耗尽后，大多数γ TuRC也会组装，但需要NEDD 1进行中心体靶向。相比之下，NEDD 1可以在γ-微管蛋白不存在的情况下靶向中心体。NEDD 1缺失的细胞显示中心体微管成核缺陷，并形成具有分离不良的两极的异常有丝分裂纺锤体。类似的纺锤体缺陷通过标记到NEDD 1的羧基末端一半的GFP融合蛋白的过表达获得，其介导与γ TuRC的结合。此外，我们发现NEDD 1的缺失抑制中心粒复制，γ-微管蛋白的缺失也是如此。我们的数据表明，中心粒复制需要NEDD 1依赖性的γ-微管蛋白募集到中心体。
The centrosome is the major microtubule organizing structure in somatic cells. Centrosomal microtubule nucleation depends on the protein γ-tubulin. In mammals, γ-tubulin associates with additional proteins into a large complex, the γ-tubulin ring complex (γTuRC). We characterize NEDD1, a centrosomal protein that associates with γTuRCs. We show that the majority of γTuRCs assemble even after NEDD1 depletion but require NEDD1 for centrosomal targeting. In contrast, NEDD1 can target to the centrosome in the absence of γ-tubulin. NEDD1-depleted cells show defects in centrosomal microtubule nucleation and form aberrant mitotic spindles with poorly separated poles. Similar spindle defects are obtained by overexpression of a fusion protein of GFP tagged to the carboxy-terminal half of NEDD1, which mediates binding to γTuRCs. Further, we show that depletion of NEDD1 inhibits centriole duplication, as does depletion of γ-tubulin. Our data suggest that centriole duplication requires NEDD1-dependent recruitment of γ-tubulin to the centrosome.