Robertson Stephen P
Department of Paediatrics and Child Health, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, New Zealand.
Curr Opin Genet Dev. 2005 Jun;15(3):301-7. doi: 10.1016/j.gde.2005.04.001.
Filamins cross-link the actin cytoskeleton into orthogonal networks and modulate the response of cells to their chemical and mechanical environment by regulating changes in shape and motility. Null mutations in FLNA, the gene that encodes filamin A, lead to defects in neuronal migration, vascular function and connective tissue integrity. By contrast, missense mutations in this same gene produce a spectrum of malformations in multiple organ systems, especially the skeleton. The production of such distinctly different phenotypes from loss- and gain-of-function mechanisms provokes questions as to how a ubiquitously expressed structural protein can subserve crucial but discrete roles during development in many organ systems.
细丝蛋白将肌动蛋白细胞骨架交联成正交网络，并通过调节细胞形状和运动性的变化来调节细胞对其化学和机械环境的反应。编码细丝蛋白A的基因FLNA中的无效突变会导致神经元迁移、血管功能和结缔组织完整性方面的缺陷。相比之下，该基因中的错义突变会在多个器官系统，尤其是骨骼中产生一系列畸形。从功能丧失和功能获得机制产生如此明显不同的表型，引发了关于一种普遍表达的结构蛋白如何在许多器官系统的发育过程中发挥关键但离散作用的问题。
