Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA.
Dev Biol. 2012 Jan 1;361(1):57-67. doi: 10.1016/j.ydbio.2011.10.010. Epub 2011 Oct 15.
Male germline stem cells (GSCs) in Drosophila melanogaster divide asymmetrically by orienting the mitotic spindle with respect to the niche, a microenvironment that specifies stem cell identity. The spindle orientation is prepared during interphase through stereotypical positioning of the centrosomes. We recently demonstrated that GSCs possess a checkpoint ("the centrosome orientation checkpoint") that monitors correct centrosome orientation prior to mitosis to ensure an oriented spindle and thus asymmetric outcome of the division. Here, we show that Par-1, a serine/threonine kinase that regulates polarity in many systems, is involved in this checkpoint. Par-1 shows a cell cycle-dependent localization to the spectrosome, a germline-specific, endoplasmic reticulum-like organelle. Furthermore, the localization of cyclin A, which is normally localized to the spectrosome, is perturbed in par-1 mutant GSCs. Interestingly, overexpression of mutant cyclin A that does not localize to the spectrosome and mutation in hts, a core component of the spectrosome, both lead to defects in the centrosome orientation checkpoint. We propose that the regulation of cyclin A localization via Par-1 function plays a critical role in the centrosome orientation checkpoint.
雄性生殖干细胞 (GSCs) 在果蝇中通过相对于小生境（一个指定干细胞身份的微环境）定位有丝分裂纺锤体来不对称分裂。纺锤体的取向在间期通过中心体的典型定位来准备。我们最近证明，GSCs 具有一个检查点（“中心体取向检查点”），该检查点在有丝分裂之前监测中心体的正确取向，以确保纺锤体的定向和因此分裂的不对称结果。在这里，我们表明 Par-1，一种调节许多系统极性的丝氨酸/苏氨酸激酶，参与了这个检查点。Par-1 表现出细胞周期依赖性定位到 spectrosome，这是一种生殖细胞特异性的内质网样细胞器。此外，cyclin A 的定位通常定位于 spectrosome，在 par-1 突变 GSCs 中受到干扰。有趣的是，突变 cyclin A 的过表达，该 cyclin A 不定位到 spectrosome 以及 hts 的突变，spectrosome 的核心组成部分，都导致中心体取向检查点的缺陷。我们提出，通过 Par-1 功能调节 cyclin A 的定位在中心体取向检查点中起着关键作用。
