Gervais Louis, Claret Sandra, Januschke Jens, Roth Siegfried, Guichet Antoine
Institut Jacques Monod, Unité Mixte de Recherche 7592, CNRS, Universités Paris 7, 2 place Jussieu, F-75251, Paris Cedex 05, France.
Development. 2008 Dec;135(23):3829-38. doi: 10.1242/dev.029009. Epub 2008 Oct 23.
The attachment of the cytoskeleton to the plasma membrane is crucial in controlling the polarized transport of cell-fate-determining molecules. Attachment involves adaptor molecules, which have the capacity to bind to both the plasma membrane and elements of the cytoskeleton, such as microtubules and actin filaments. Using the Drosophila oocyte as a model system, we show that the type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K), Skittles, is necessary to sustain the organization of microtubules and actin cytoskeleton required for the asymmetric transport of oskar, bicoid and gurken mRNAs and thereby controls the establishment of cell polarity. We show that Skittles function is crucial to synthesize and maintain phosphatidylinositol 4,5 bisphosphate (PIP2) at the plasma membrane in the oocyte. Reduction of Skittles activity impairs activation at the plasma membrane of Moesin, a member of the ERM family known to link the plasma membrane to the actin-based cytoskeleton. Furthermore, we provide evidence that Skittles, by controlling the localization of Bazooka, Par-1 and Lgl, but not Lkb1, to the cell membrane, regulates PAR polarity proteins and the maintenance of specific cortical domains along the anteroposterior axis.
细胞骨架与质膜的附着对于控制细胞命运决定分子的极性运输至关重要。这种附着涉及衔接分子，它们能够同时结合质膜和细胞骨架成分，如微管和肌动蛋白丝。以果蝇卵母细胞作为模型系统，我们发现I型磷脂酰肌醇4-磷酸5-激酶（PIP5K）“Skittles”对于维持osk、bico和gur mRNA不对称运输所需的微管和肌动蛋白细胞骨架的组织是必要的，从而控制细胞极性的建立。我们表明，“Skittles”的功能对于在卵母细胞质膜上合成和维持磷脂酰肌醇4,5-二磷酸（PIP2）至关重要。“Skittles”活性的降低会损害膜突蛋白（Moesin）在质膜上的激活，膜突蛋白是ERM家族的一员，已知其将质膜与基于肌动蛋白的细胞骨架相连。此外，我们提供证据表明，“Skittles”通过控制“Bazooka”、“Par-1”和“Lgl”（而非“Lkb1”）在细胞膜上的定位，调节PAR极性蛋白以及沿前后轴特定皮质结构域的维持。
