Zhang Renshuai, Tang Jianming, Li Tianliang, Zhou Jun, Pan Wei
Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Sciences, Institute of Biomedical Sciences, Shandong Normal University, Jinan, China.
Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang, China.
Front Mol Biosci. 2022 Apr 6;9:885592. doi: 10.3389/fmolb.2022.885592. eCollection 2022.
Primary cilia are ubiquitous mechanosensory organelles that specifically coordinate a series of cellular signal transduction pathways to control cellular physiological processes during development and in tissue homeostasis. Defects in the function or structure of primary cilia have been shown to be associated with a large range of diseases called ciliopathies. Inositol polyphosphate-5-phosphatase E (INPP5E) is an inositol polyphosphate 5-phosphatase that is localized on the ciliary membrane by anchorage via its C-terminal prenyl moiety and hydrolyzes both phosphatidylinositol-4, 5-bisphosphate (PtdIns(4,5)P) and PtdIns(3,4,5)P, leading to changes in the phosphoinositide metabolism, thereby resulting in a specific phosphoinositide distribution and ensuring proper localization and trafficking of proteins in primary cilia. In addition, INPP5E also works synergistically with cilia membrane-related proteins by playing key roles in the development and maintenance homeostasis of cilia. The mutation of INPP5E will cause deficiency of primary cilia signaling transduction, ciliary instability and ciliopathies. Here, we present an overview of the role of INPP5E and its coordination of signaling networks in primary cilia.
初级纤毛是普遍存在的机械感觉细胞器，在发育过程和组织稳态中，它能特异性地协调一系列细胞信号转导通路，以控制细胞生理过程。初级纤毛功能或结构的缺陷已被证明与一大类称为纤毛病的疾病有关。肌醇多磷酸-5-磷酸酶E（INPP5E）是一种肌醇多磷酸5-磷酸酶，通过其C末端异戊二烯基部分锚定在纤毛膜上，水解磷脂酰肌醇-4,5-二磷酸（PtdIns(4,5)P）和PtdIns(3,4,5)P，导致磷酸肌醇代谢发生变化，从而产生特定的磷酸肌醇分布，并确保蛋白质在初级纤毛中的正确定位和运输。此外，INPP5E还通过在纤毛的发育和维持稳态中发挥关键作用，与纤毛膜相关蛋白协同工作。INPP5E的突变将导致初级纤毛信号转导缺陷、纤毛不稳定和纤毛病。在此，我们概述了INPP5E的作用及其在初级纤毛中对信号网络的协调作用。
