Okada Kyoko, Bartolini Francesca, Deaconescu Alexandra M, Moseley James B, Dogic Zvonimir, Grigorieff Nikolaus, Gundersen Gregg G, Goode Bruce L
Department of Biology, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA.
J Cell Biol. 2010 Jun 28;189(7):1087-96. doi: 10.1083/jcb.201001016. Epub 2010 Jun 21.
The tumor suppressor protein adenomatous polyposis coli (APC) regulates cell protrusion and cell migration, processes that require the coordinated regulation of actin and microtubule dynamics. APC localizes in vivo to microtubule plus ends and actin-rich cortical protrusions, and has well-documented direct effects on microtubule dynamics. However, its potential effects on actin dynamics have remained elusive. Here, we show that the C-terminal "basic" domain of APC (APC-B) potently nucleates the formation of actin filaments in vitro and stimulates actin assembly in cells. Nucleation is achieved by a mechanism involving APC-B dimerization and recruitment of multiple actin monomers. Further, APC-B nucleation activity is synergistic with its in vivo binding partner, the formin mDia1. Together, APC-B and mDia1 overcome a dual cellular barrier to actin assembly imposed by profilin and capping protein. These observations define a new function for APC and support an emerging view of collaboration between distinct actin assembly-promoting factors with complementary activities.
肿瘤抑制蛋白腺瘤性息肉病大肠杆菌（APC）调节细胞突起和细胞迁移，这些过程需要对肌动蛋白和微管动力学进行协调调节。APC在体内定位于微管正端和富含肌动蛋白的皮质突起，并且对微管动力学具有充分记录的直接影响。然而，其对肌动蛋白动力学的潜在影响仍然难以捉摸。在这里，我们表明APC的C末端“碱性”结构域（APC-B）在体外有力地促进肌动蛋白丝的形成，并在细胞中刺激肌动蛋白组装。成核是通过一种涉及APC-B二聚化和募集多个肌动蛋白单体的机制实现的。此外，APC-B成核活性与其体内结合伴侣formin mDia1具有协同作用。总之，APC-B和mDia1克服了由肌动蛋白结合蛋白和封端蛋白对肌动蛋白组装造成的双重细胞障碍。这些观察结果定义了APC的新功能，并支持了具有互补活性的不同肌动蛋白组装促进因子之间合作的新观点。
