Adada Mohamad, Canals Daniel, Hannun Yusuf A, Obeid Lina M
The Department of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
The Department of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; The Northport VA Medical Center, Northport, NY 11768, USA.
Biochim Biophys Acta. 2014 May;1841(5):727-37. doi: 10.1016/j.bbalip.2013.07.002. Epub 2013 Jul 12.
A key but poorly studied domain of sphingolipid functions encompasses endocytosis, exocytosis, cellular trafficking, and cell movement. Recently, the ezrin, radixin and moesin (ERM) family of proteins emerged as novel potent targets regulated by sphingolipids. ERMs are structural proteins linking the actin cytoskeleton to the plasma membrane, also forming a scaffold for signaling pathways that are used for cell proliferation, migration and invasion, and cell division. Opposing functions of the bioactive sphingolipid ceramide and sphingosine-1-phosphate (S1P), contribute to ERM regulation. S1P robustly activates whereas ceramide potently deactivates ERM via phosphorylation/dephosphorylation, respectively. This recent dimension of cytoskeletal regulation by sphingolipids opens up new avenues to target cell dynamics, and provides further understanding of some of the unexplained biological effects mediated by sphingolipids. In addition, these studies are providing novel inroads into defining basic mechanisms of regulation and action of bioactive sphingolipids. This review describes the current understanding of sphingolipid regulation of the cytoskeleton, it also describes the biologies in which ERM proteins have been involved, and finally how these two large fields have started to converge. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.
鞘脂功能中一个关键但研究较少的领域包括内吞作用、外排作用、细胞运输和细胞运动。最近，埃兹蛋白、根蛋白和膜突蛋白（ERM）家族蛋白成为受鞘脂调节的新的重要靶点。ERM是将肌动蛋白细胞骨架与质膜相连的结构蛋白，也为用于细胞增殖、迁移和侵袭以及细胞分裂的信号通路形成支架。生物活性鞘脂神经酰胺和1-磷酸鞘氨醇（S1P）的相反功能有助于ERM调节。S1P通过磷酸化分别强烈激活ERM，而神经酰胺通过去磷酸化有效使其失活。鞘脂对细胞骨架调节的这一最新层面为靶向细胞动力学开辟了新途径，并进一步理解了鞘脂介导的一些无法解释的生物学效应。此外，这些研究为确定生物活性鞘脂的调节和作用基本机制提供了新的切入点。本综述描述了目前对鞘脂调节细胞骨架的理解，还描述了ERM蛋白所涉及的生物学过程，最后阐述了这两个大领域是如何开始融合的。本文是名为“鞘脂生物学新前沿”特刊的一部分。
