Oriolo Andrea S, Wald Flavia A, Ramsauer Victoria P, Salas Pedro J I
Department of Cell Biology and Anatomy, University of Miami, Miller School of Medicine, 1600 NW 10th Ave.-RMSB, Miami, FL 33136, USA.
Exp Cell Res. 2007 Jun 10;313(10):2255-64. doi: 10.1016/j.yexcr.2007.02.030. Epub 2007 Mar 12.
Intermediate filaments have long been considered mechanical components of the cell that provide resistance to deformation stress. Practical experimental problems, including insolubility, lack of good pharmacological antagonists, and the paucity of powerful genetic models have handicapped the research of other functions. In single-layered epithelial cells, keratin intermediate filaments are cortical, either apically polarized or apico-lateral. This review analyzes phenotypes of genetic manipulations of simple epithelial cell keratins in mice and Caenorhabditis elegans that strongly suggest a role of keratins in apico-basal polarization and membrane traffic. Published evidence that intermediate filaments can act as scaffolds for proteins involved in membrane traffic and signaling is also discussed. Such a scaffolding function would generate a highly polarized compartment within the cytoplasm of simple epithelial cells. While in most cases mechanistic explanations for the keratin-null or overexpression phenotypes are still missing, it is hoped that investigators will be encouraged to study these as yet poorly understood functions of intermediate filaments.
中间丝长期以来一直被认为是细胞的机械组成部分,能够抵抗变形应力。实际的实验问题,包括不溶性、缺乏良好的药理学拮抗剂以及强大的遗传模型的匮乏,阻碍了对其他功能的研究。在单层上皮细胞中,角蛋白中间丝位于皮质,要么顶端极化,要么顶端-侧面极化。这篇综述分析了小鼠和秀丽隐杆线虫中简单上皮细胞角蛋白基因操作的表型,这些表型强烈表明角蛋白在顶端-基部极化和膜运输中发挥作用。还讨论了已发表的证据,即中间丝可以作为参与膜运输和信号传导的蛋白质的支架。这种支架功能将在简单上皮细胞的细胞质内产生一个高度极化的区室。虽然在大多数情况下,对角蛋白缺失或过表达表型的机制解释仍然缺失,但希望能鼓励研究人员研究中间丝这些尚未被充分理解的功能。