Kim Kwonseop, Sirota Anna, Chen Yh Yan-hua, Jones Shiloh B, Dudek Ronald, Lanford George W, Thakore Chittam, Lu Qun
Department of Anatomy and Cell Biology, The Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA.
Exp Cell Res. 2002 May 1;275(2):171-84. doi: 10.1006/excr.2002.5503.
Actin- and microtubule-mediated changes in cell shape are essential for many cellular activities. However, the molecular mechanisms underlying the interplay between the two are complex and remain obscure. Here we show that the expression of delta-catenin (or NPRAP/Neurojungin), a member of p120(ctn) subfamily of armadillo proteins can induce the branching of dendrite-like processes in 3T3 cells and enhance dendritic morphogenesis in primary hippocampal neurons. This induction of branching phenotype involves initially the disruption of filamentous actin, and requires the growth of microtubules. The carboxyl-terminal truncation mutant of delta-catenin can cluster and redistribute the full-length protein, and dominantly inhibit its branching effect. delta-Catenin forms protein complexes and can bind directly to actin in vitro. The carboxyl-terminal truncation of delta-catenin does not interfere with its actin-binding capability; therefore the actin interaction alone is not sufficient for the induction of dendrite-like processes. When delta-catenin-transformed cells establish elaborate dendrite-like branches, the main cellular processes become stabilized and resist the disruption of both actin filaments and microtubules, as determined by fluorescent light microscopy and time-lapse recording analyses. We suggest that delta-catenin can effect a biphasic cytoskeletal remodeling event which differentially regulates actin and microtubules and promotes cellular morphogenesis.
肌动蛋白和微管介导的细胞形状变化对许多细胞活动至关重要。然而，两者之间相互作用的分子机制复杂且仍不清楚。在此我们表明，犰狳蛋白p120（ctn）亚家族成员δ-连环蛋白（或NPRAP/Neurojungin）的表达可诱导3T3细胞中树突状突起分支，并增强原代海马神经元的树突形态发生。这种分支表型的诱导最初涉及丝状肌动蛋白的破坏，并且需要微管的生长。δ-连环蛋白的羧基末端截短突变体可聚集并重新分布全长蛋白，并显性抑制其分支效应。δ-连环蛋白形成蛋白复合物，并且在体外可直接与肌动蛋白结合。δ-连环蛋白的羧基末端截短并不干扰其与肌动蛋白的结合能力；因此，仅肌动蛋白相互作用不足以诱导树突状突起。当δ-连环蛋白转化的细胞形成精细的树突状分支时，主要细胞突起变得稳定，并抵抗肌动蛋白丝和微管的破坏，这通过荧光显微镜和延时记录分析得以确定。我们认为，δ-连环蛋白可引发双相细胞骨架重塑事件，该事件以不同方式调节肌动蛋白和微管，并促进细胞形态发生。
