Hoogenraad Casper C, Akhmanova Anna, Galjart Niels, De Zeeuw Chris I
Department of Neuroscience, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Bioessays. 2004 Feb;26(2):141-50. doi: 10.1002/bies.10402.
Williams Syndrome is a developmental disorder that is characterized by cardiovascular problems, particular facial features and several typical behavioral and neurological abnormalities. In Williams Syndrome patients, a heterozygous deletion is present of a region on chromosome 7q11.23 (the Williams Syndrome critical region), which spans approximately 20 genes. Two of these genes encode proteins that regulate dynamic aspects of the cytoskeleton of the cell, either via the actin filament system (LIM kinase 1, or LIMK1), or through the microtubule network (cytoplasmic linker protein of 115 kDa, or CLIP-115). The recent findings that knockout mice lacking LIMK1 or CLIP-115 have distinct neurological and behavioural phenotypes, indicates that cytoskeletal defects might play a role in the development of neurological symptoms in Williams Syndrome patients. In this review, we discuss the properties of LIMK and CLIP family proteins, their function in the regulation of the actin and microtubule cytoskeletal systems, respectively, and the relationship with neurodevelopmental aspects of Williams Syndrome.
威廉姆斯综合征是一种发育障碍疾病，其特征为心血管问题、独特的面部特征以及一些典型的行为和神经异常。在威廉姆斯综合征患者中，7号染色体q11.23区域（威廉姆斯综合征关键区域）存在杂合性缺失，该区域大约包含20个基因。其中两个基因编码的蛋白质可通过肌动蛋白丝系统（LIM激酶1，即LIMK1）或微管网络（115 kDa的细胞质连接蛋白，即CLIP-115）来调节细胞骨架的动态特性。最近的研究发现，缺乏LIMK1或CLIP-115的基因敲除小鼠具有明显的神经和行为表型，这表明细胞骨架缺陷可能在威廉姆斯综合征患者神经症状的发展中起作用。在这篇综述中，我们讨论了LIMK和CLIP家族蛋白的特性、它们分别在调节肌动蛋白和微管细胞骨架系统中的功能，以及与威廉姆斯综合征神经发育方面的关系。
