Nakamura T, Takeuchi K, Muraoka S, Takezoe H, Takahashi N, Mori N
Biomedical R & D Department, Sumitomo Electric Industries, Sakae-ku, Yokohama 244-8588, Japan.
J Biol Chem. 1999 May 7;274(19):13322-7. doi: 10.1074/jbc.274.19.13322.
Brain-enriched human FC96 protein shows a close sequence similarity to the Dictyostelium actin-binding protein coronin, which has been implicated in cell motility, cytokinesis, and phagocytosis. A phylogenetic tree analysis revealed that FC96 and two other mammalian molecules (p57 and IR10) form a new protein family, the coronin-like protein (Clipin) family; thus hereafter we refer to FC96 as ClipinC. A WD domain and a succeeding alpha-helical region are conserved among coronin and Clipin family members. ClipinC is predominantly expressed in the brain, and discrete areas in the mouse brain were intensely labeled with anti-ClipinC antibodies. ClipinC was also shown to bind directly to F-actin in vitro. Immunocytochemical analysis revealed that ClipinC accumulated at focal adhesions as well as at neurite tips and stress fibers. Furthermore, ClipinC was associated with vinculin, which is a major component of focal contacts. These results indicate that ClipinC is also a component part of the cross-bridge between the actin cytoskeleton and the plasma membrane. These findings and the previously reported function of coronin suggest that ClipinC may play specific roles in the reorganization of neuronal actin structure, a change that has been implicated in both cell motility and growth cone advance.
富含大脑的人类FC96蛋白与盘基网柄菌肌动蛋白结合蛋白冠蛋白显示出紧密的序列相似性，冠蛋白与细胞运动、胞质分裂和吞噬作用有关。系统发育树分析表明，FC96和其他两个哺乳动物分子（p57和IR10）形成了一个新的蛋白质家族，即类冠蛋白（Clipin）家族；因此，我们此后将FC96称为ClipinC。WD结构域和随后的α螺旋区域在冠蛋白和Clipin家族成员中是保守的。ClipinC主要在大脑中表达，小鼠大脑中的离散区域被抗ClipinC抗体强烈标记。体外实验还表明ClipinC能直接与F-肌动蛋白结合。免疫细胞化学分析显示，ClipinC在粘着斑以及神经突尖端和应力纤维处积累。此外，ClipinC与纽蛋白相关，纽蛋白是粘着斑的主要成分。这些结果表明，ClipinC也是肌动蛋白细胞骨架和质膜之间交叉桥的组成部分。这些发现以及先前报道的冠蛋白功能表明，ClipinC可能在神经元肌动蛋白结构的重组中发挥特定作用，这种变化与细胞运动和生长锥前进都有关。
