Yoder Michael, Hildebrand Jeffrey D
Department of Biological Sciences, University of Pittsburgh, 4249 Fifth Avenue, Pittsburgh, PA 15260, USA.
Cell Motil Cytoskeleton. 2007 Jan;64(1):49-63. doi: 10.1002/cm.20167.
All animal cells utilize a specialized set of cytoskeletal proteins to determine their overall shape and the organization of their intracellular compartments and organelles. During embryonic development, the dynamic nature of the actin cytoskeleton is critical for virtually all morphogenic events requiring changes in cell shape, migration, adhesion, and division. The behavior of the actin cytoskeleton is modulated by a myriad of accessory proteins. Shroom3 is an actin binding protein that regulates neural tube morphogenesis by eliciting changes in cell shape through a myosin II-dependent pathway. The Shroom-related gene SHROOM4 (formerly called KIAA1202) has also been implicated in neural development, as mutations in this gene are associated with human X-linked mental retardation. To better understand the function of Shrm4 in embryonic development, we have cloned mouse Shroom4 and characterized its protein product in vivo and in vitro. Shroom4 is expressed in a wide range of cell types during mouse development, including vascular endothelium and the polarized epithelium of the neural tube and kidney. In endothelial cells and embryo fibroblasts, endogenous Shroom4 co-distributes with myosin II to a distinct cytoplasmic population of F-actin and ectopic expression of Shroom4 in multiple cell types enhances or induces the formation of this actin-based structure. This localization is mediated, at least in part, by the direct interaction of Shroom4 and F-actin. Our results suggest that Shroom4 is a regulator of cytoskeletal architecture that may play an important role in vertebrate development.
所有动物细胞都利用一组特殊的细胞骨架蛋白来确定其整体形状以及细胞内区室和细胞器的组织方式。在胚胎发育过程中,肌动蛋白细胞骨架的动态性质对于几乎所有需要细胞形状、迁移、黏附和分裂发生变化的形态发生事件都至关重要。肌动蛋白细胞骨架的行为受到众多辅助蛋白的调节。Shroom3是一种肌动蛋白结合蛋白,它通过依赖肌球蛋白II的途径引发细胞形状变化,从而调节神经管形态发生。与Shroom相关的基因SHROOM4(以前称为KIAA1202)也与神经发育有关,因为该基因的突变与人类X连锁智力迟钝相关。为了更好地理解Shrm4在胚胎发育中的功能,我们克隆了小鼠Shroom4,并在体内和体外对其蛋白产物进行了表征。Shroom4在小鼠发育过程中的多种细胞类型中表达,包括血管内皮以及神经管和肾脏的极化上皮。在内皮细胞和胚胎成纤维细胞中,内源性Shroom4与肌球蛋白II共同分布于F-肌动蛋白的一个独特细胞质群体中,并且Shroom4在多种细胞类型中的异位表达增强或诱导了这种基于肌动蛋白的结构的形成。这种定位至少部分是由Shroom4与F-肌动蛋白的直接相互作用介导的。我们的结果表明,Shroom4是细胞骨架结构的调节因子,可能在脊椎动物发育中起重要作用。