Soung Nak-Kyun, Park Jung-Eun, Yu Li-Rong, Lee Kyung H, Lee Jung-Min, Bang Jeong K, Veenstra Timothy D, Rhee Kunsoo, Lee Kyung S
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Dev Cell. 2009 Apr;16(4):539-50. doi: 10.1016/j.devcel.2009.02.004.
Outer dense fiber 2 (ODF2) was initially identified as a major component of the sperm tail cytoskeleton, and was later suggested to be localized to somatic centrosomes and required for the formation of primary cilia. Here we show that a splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently localizes to somatic centrosomes via a variant-specific C-terminal extension and recruits Plk1 through a Cdc2-dependent phospho-S796 motif within the extension. This interaction and Plk1 activity were important for proper recruitment of pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar spindles. Earlier in the cell cycle, hCenexin1, but again not hODF2, also contributed to centrosomal recruitment of ninein and primary cilia formation independent of Plk1 interaction. These findings provide a striking example of how a splice-generated C-terminal extension of a sperm tail-associating protein mediates unanticipated centrosomal events at distinct stages of the somatic cell cycle.
外致密纤维2（ODF2）最初被鉴定为精子尾部细胞骨架的主要成分，后来有人提出它定位于体细胞中心体，是初级纤毛形成所必需的。在这里，我们表明，hODF2的一个剪接变体hCenexin1，而不是hODF2本身，通过一个变体特异性的C末端延伸有效地定位于体细胞中心体，并通过该延伸内一个依赖Cdc2的磷酸化S796基序招募Plk1。这种相互作用和Plk1活性对于中心粒外周蛋白和γ-微管蛋白的正确募集很重要，最终对于正常双极纺锤体的形成也很重要。在细胞周期的早期，hCenexin1，但同样不是hODF2，也独立于Plk1相互作用促进了九蛋白在中心体的募集和初级纤毛的形成。这些发现提供了一个引人注目的例子，说明精子尾部相关蛋白的剪接产生的C末端延伸如何在体细胞周期的不同阶段介导意外的中心体事件。
