Identification of a human centrosomal calmodulin-binding protein that shares homology with pericentrin

Identification of a human centrosomal calmodulin-binding protein that shares homology with pericentrin
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DOI:
10.1073/pnas.97.11.5919
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发表时间:
2000-05-23
影响因子:
11.1
通讯作者:
Davis, TN
Davis, TN
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Flory, MR;Moser, MJ;Davis, TN

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真核生物的染色体分离依赖于有丝分裂纺锤体,一种由中心体成核的双极性微管阵列。中心体微管成核需要γ -微管蛋白环复合物附着在盐不溶性中心体核心上,但这种附着的潜在因素尚不清楚。在出芽酵母中,这种附着是由螺旋状蛋白Spc110p提供的,它将酵母γ -微管蛋白复合物连接到酵母中心体的核心。在这里,我们证明了大卷曲卷曲蛋白kendrin是Spc110p的人类同源物。我们通过其c端钙调素结合位点鉴定了kendrin,该位点与Spc110p钙调素结合位点具有同源性。Kendrin在整个细胞周期中特异定位于中心体。kendrin的n端区域与周心蛋白具有显著的序列同源性,周心蛋白是一种已知与γ -微管蛋白相互作用的小鼠中心体成分。在有丝分裂的人乳腺癌细胞中含有丰富的中心体样结构,kendrin仅在与纺锤体微管相关的中心体中发现。
Eukaryotic chromosome segregation depends on the mitotic spindle apparatus, a bipolar array of microtubules nucleated from centrosomes. Centrosomal microtubule nucleation requires attachment of gamma-tubulin ring complexes to a salt-insoluble centrosomal core, but the factor(s) underlying this attachment remains unknown. In budding yeast, this attachment is provided by the coiled-coil protein Spc110p, which links the yeast gamma-tubulin complex to the core of the yeast centrosome. Here, we show that the large coiled-coil protein kendrin is a human orthologue of Spc110p. We identified kendrin by its C-terminal calmodulin-binding site, which shares homology with the Spc110p calmodulin-binding site. Kendrin localizes specifically to centrosomes throughout the cell cycle. N-terminal regions of kendrin share significant sequence homology with pericentrin, a previously identified murine centrosome component known to interact with gamma-tubulin. In mitotic human breast carcinoma cells containing abundant centrosome-like structures, kendrin is found only at centrosomes associated with spindle microtubules.