*Division of Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
Biochem Soc Trans. 2013 Dec;41(6):1605-12. doi: 10.1042/BST20130188.
Neurons are highly specialized for the processing and transmission of electrical signals and use cytoskeleton-based motor proteins to transport different vesicles and cellular materials. Abnormalities in intracellular transport are thought to be a critical factor in the degeneration and death of neurons in both the central and peripheral nervous systems. Several recent studies describe disruptive mutations in the minus-end-directed microtubule motor cytoplasmic dynein that are directly linked to human motor neuropathies, such as SMA (spinal muscular atrophy) and axonal CMT (Charcot-Marie-Tooth) disease or malformations of cortical development, including lissencephaly, pachygyria and polymicrogyria. In addition, genetic defects associated with these and other neurological disorders have been found in multifunctional adaptors that regulate dynein function, including the dynactin subunit p150(Glued), BICD2 (Bicaudal D2), Lis-1 (lissencephaly 1) and NDE1 (nuclear distribution protein E). In the present paper we provide an overview of the disease-causing mutations in dynein motors and regulatory proteins that lead to a broad phenotypic spectrum extending from peripheral neuropathies to cerebral malformations.
神经元高度特化于处理和传递电信号，并利用基于细胞骨架的运动蛋白来运输不同的囊泡和细胞物质。细胞内运输的异常被认为是中枢和周围神经系统中神经元退化和死亡的一个关键因素。最近的几项研究描述了负向微管马达细胞质动力蛋白的破坏性突变，这些突变与人类运动神经病直接相关，如 SMA（脊髓性肌萎缩症）和轴索性 CMT（Charcot-Marie-Tooth）疾病，或皮质发育畸形，包括无脑回畸形、巨脑回畸形和多微脑回畸形。此外，与这些和其他神经疾病相关的遗传缺陷已在调节动力蛋白功能的多功能衔接蛋白中被发现，包括 dynactin 亚基 p150(Glued)、BICD2 (Bicaudal D2)、Lis-1 (无脑回畸形 1) 和 NDE1 (核分布蛋白 E)。在本文中，我们概述了导致广泛表型谱的动力蛋白和调节蛋白的致病突变，该表型谱从周围神经病延伸到脑畸形。
