Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
FEBS Lett. 2012 Aug 31;586(18):2846-57. doi: 10.1016/j.febslet.2012.07.037. Epub 2012 Jul 22.
Phosphoinositides regulate numerous cellular events via the recruitment and activation of multiple lipid-binding effector proteins. The precise temporal and spatial regulation of phosphoinositide signals by the co-ordinated activities of phosphoinositide kinases and phosphatases is essential for homeostasis and development. Mutations in two inositol polyphosphate 5-phosphatases, INPP5E and OCRL, cause the cerebrorenal syndromes of Joubert and Lowe's, respectively. INPP5E and OCRL exhibit overlapping phosphoinositide substrate specificity and subcellular localisation, including an association with the primary cilia. Here, we review recent studies that identify a new role for these enzymes in the regulation of primary cilia function. Joubert syndrome has been extensively linked to primary cilia defects, and Lowe's may represent a new class of 'ciliopathy associated' syndromes.
磷酸肌醇调节多种细胞事件，通过招募和激活多种脂结合效应蛋白。磷酸肌醇激酶和磷酸酶的协调活动对磷酸肌醇信号的精确时空调节对于体内平衡和发育至关重要。两种肌醇多磷酸 5-磷酸酶 INPP5E 和 OCRL 的突变分别导致杰伯特和洛氏脑肾综合征。INPP5E 和 OCRL 表现出重叠的磷酸肌醇底物特异性和亚细胞定位，包括与初级纤毛的关联。在这里，我们回顾了最近的研究，这些研究确定了这些酶在调节初级纤毛功能中的新作用。杰伯特综合征与初级纤毛缺陷密切相关，而洛氏可能代表一类新的“纤毛病相关”综合征。
