Ikeda W, Nakanishi H, Takekuni K, Itoh S, Takai Y
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, 565-0871, Japan.
Biochem Biophys Res Commun. 2001 Sep 7;286(5):1066-72. doi: 10.1006/bbrc.2001.5481.
Frabin is a GDP/GTP exchange protein for Cdc42 small G protein with actin filament-binding activity. Frabin consists of the actin filament-binding domain, the Dbl homology domain, the first pleckstrin homology domain, the FYVE-finger domain, and the second pleckstrin homology domain in this order from the N-terminus. Frabin forms filopodia through direct activation of Cdc42 and lamellipodia through indirect activation of Rac small G protein. We isolated here two smaller splicing variants of frabin and named the original one, middle-size one, and smallest one frabin-alpha, -beta, and -gamma, respectively. Frabin-beta lacked the second pleckstrin homology domain and frabin-gamma lacked the FYVE-finger domain and the second pleckstrin homology domain. These three variants were expressed in all of the tissues examined but their expression levels are different depending on tissues. In L fibroblasts, all the three variants formed filopodia. As to lamellipodia, frabin-alpha formed them; frabin-beta formed them to a small extent; and frabin-gamma did not. In MDCK epithelial cells, frabin-alpha formed microspikes but frabin-beta or -gamma did not.
Frabin是一种针对Cdc42小G蛋白的GDP/GTP交换蛋白，具有肌动蛋白丝结合活性。Frabin从N端起依次由肌动蛋白丝结合结构域、Dbl同源结构域、第一个普列克底物蛋白同源结构域、FYVE指状结构域和第二个普列克底物蛋白同源结构域组成。Frabin通过直接激活Cdc42形成丝状伪足，并通过间接激活Rac小G蛋白形成片状伪足。我们在此分离出了两种较小的frabin剪接变体，分别将原始的、中等大小的和最小的变体命名为frabin-α、-β和-γ。Frabin-β缺少第二个普列克底物蛋白同源结构域，frabin-γ缺少FYVE指状结构域和第二个普列克底物蛋白同源结构域。这三种变体在所有检测的组织中均有表达，但它们的表达水平因组织而异。在L成纤维细胞中，所有这三种变体都能形成丝状伪足。至于片状伪足，frabin-α能形成；frabin-β能少量形成；而frabin-γ则不能。在MDCK上皮细胞中，frabin-α能形成微棘，而frabin-β或-γ则不能。
