Ramkumar Amrita, Jong Brigette Y, Ori-McKenney Kassandra M
Department of Molecular and Cellular Biology, University of California, Davis, CA.
Dev Dyn. 2018 Jan;247(1):138-155. doi: 10.1002/dvdy.24599. Epub 2017 Oct 27.
Classical microtubule-associated proteins (MAPs) were originally identified based on their co-purification with microtubules assembled from mammalian brain lysate. They have since been found to perform a range of functions involved in regulating the dynamics of the microtubule cytoskeleton. Most of these MAPs play integral roles in microtubule organization during neuronal development, microtubule remodeling during neuronal activity, and microtubule stabilization during neuronal maintenance. As a result, mutations in MAPs contribute to neurodevelopmental disorders, psychiatric conditions, and neurodegenerative diseases. MAPs are post-translationally regulated by phosphorylation depending on developmental time point and cellular context. Phosphorylation can affect the microtubule affinity, cellular localization, or overall function of a particular MAP and can thus have profound implications for neuronal health. Here we review MAP1, MAP2, MAP4, MAP6, MAP7, MAP9, tau, and DCX, and how each is regulated by phosphorylation in neuronal physiology and disease. Developmental Dynamics 247:138-155, 2018. © 2017 Wiley Periodicals, Inc.
经典的微管相关蛋白(MAPs)最初是根据它们与从哺乳动物脑裂解物组装的微管共纯化而鉴定出来的。此后,人们发现它们具有一系列参与调节微管细胞骨架动力学的功能。这些MAPs中的大多数在神经元发育过程中的微管组织、神经元活动期间的微管重塑以及神经元维持期间的微管稳定中发挥不可或缺的作用。因此,MAPs中的突变会导致神经发育障碍、精神疾病和神经退行性疾病。MAPs在翻译后受磷酸化调节,具体取决于发育时间点和细胞环境。磷酸化可以影响特定MAP的微管亲和力、细胞定位或整体功能,因此可能对神经元健康产生深远影响。在这里,我们综述了MAP1、MAP2、MAP4、MAP6、MAP7、MAP9、tau和双皮质素(DCX),以及它们在神经元生理和疾病中如何通过磷酸化进行调节。《发育动力学》247:138 - 155,2018年。© 2017威利期刊公司。