Compartimentation et Dynamique Cellulaires, CNRS, UMR144 Paris F-75248, France.
J Cell Sci. 2011 Apr 1;124(Pt 7):1156-66. doi: 10.1242/jcs.076711.
The LIM-domain protein Ajuba localizes at sites of epithelial cell-cell adhesion and has also been implicated in the activation of Aurora-A (Aur-A). Despite the expected importance of Ajuba, Ajuba-deficient mice are viable, which has been attributed to functional redundancy with the related LIM-domain protein LIMD1. To gain insights into the function of Ajuba, we investigated its role in Drosophila, where a single gene (jub) encodes a protein closely related to Ajuba and LIMD1. We identified a key function in neural stem cells, where Jub localizes to the centrosome. In these cells, mutation in jub leads to centrosome separation defects and aberrant mitotic spindles, which is a phenotype similar to that of aur-A mutants. We show that in jub mutants Aur-A activity is not perturbed, but that Aur-A recruitment and maintenance at the centrosome is affected. As a consequence the active kinase is displaced from the centrosome. On the basis of our studies in Drosophila neuroblasts, we propose that a key function of Ajuba, in these cells, is to maintain active Aur-A at the centrosome during mitosis.
LIM 结构域蛋白 Ajuba 定位于上皮细胞-细胞黏附部位，并且还与 Aurora-A（Aur-A）的激活有关。尽管 Ajuba 具有预期的重要性，但 Ajuba 缺陷型小鼠是存活的，这归因于与相关的 LIM 结构域蛋白 LIMD1 的功能冗余。为了深入了解 Ajuba 的功能，我们在果蝇中研究了它的作用，其中单个基因（jub）编码与 Ajuba 和 LIMD1 密切相关的蛋白质。我们确定了在神经干细胞中的一个关键功能，其中 Jub 定位于中心体。在这些细胞中，jub 突变导致中心体分离缺陷和异常有丝分裂纺锤体，这是类似于 aur-A 突变体的表型。我们表明，在 jub 突变体中 Aur-A 活性未受到干扰，但 Aur-A 募集和维持在中心体受到影响。因此，活性激酶从中心体移位。基于我们在果蝇神经母细胞瘤中的研究，我们提出，Ajuba 的一个关键功能是在有丝分裂期间将活性 Aur-A 维持在中心体上。
