Magdalena Juana, Millard Thomas H, Etienne-Manneville Sandrine, Launay Sophie, Warwick Helen K, Machesky Laura M
School of Biosciences, University of Birmingham, Edgbaston, United Kingdom.
Mol Biol Cell. 2003 Feb;14(2):670-84. doi: 10.1091/mbc.e02-06-0345.
Cell motility and cell polarity are essential for morphogenesis, immune system function, and tissue repair. Many animal cells move by crawling, and one main driving force for movement is derived from the coordinated assembly and disassembly of actin filaments. As tissue culture cells migrate to close a scratch wound, this directional extension is accompanied by Golgi apparatus reorientation, to face the leading wound edge, giving the motile cell inherent polarity aligned relative to the wound edge and to the direction of cell migration. Cellular proteins essential for actin polymerization downstream of Rho family GTPases include the Arp2/3 complex as an actin nucleator and members of the Wiskott-Aldrich Syndrome protein (WASP) family as activators of the Arp2/3 complex. We therefore analyzed the involvement of the Arp2/3 complex and WASP-family proteins in in vitro wound healing assays using NIH 3T3 fibroblasts and astrocytes. In NIH 3T3 cells, we found that actin and Arp2/3 complex contributed to cell polarity establishment. Moreover, overexpression of N-terminal fragments of Scar2 (but not N-WASP or Scar1 or Scar3) interfere with NIH 3T3 Golgi polarization but not with cell migration. In contrast, actin, Arp2/3, and WASP-family proteins did not appear to be involved in Golgi polarization in astrocytes. Our results thus indicate that the requirement for Golgi polarity establishment is cell-type specific. Furthermore, in NIH 3T3 cells, Scar2 and the Arp2/3 complex appear to be involved in the establishment and maintenance of Golgi polarity during directed migration.
细胞运动性和细胞极性对于形态发生、免疫系统功能及组织修复至关重要。许多动物细胞通过爬行移动,运动的一个主要驱动力源自肌动蛋白丝的协同组装与拆卸。当组织培养细胞迁移以闭合划痕伤口时,这种定向延伸伴随着高尔基体重新定向,使其面向伤口前沿,赋予运动细胞相对于伤口边缘及细胞迁移方向的固有极性。Rho家族GTP酶下游肌动蛋白聚合所必需的细胞蛋白包括作为肌动蛋白成核剂的Arp2/3复合物以及作为Arp2/3复合物激活剂的威斯科特-奥尔德里奇综合征蛋白(WASP)家族成员。因此,我们使用NIH 3T3成纤维细胞和星形胶质细胞在体外伤口愈合试验中分析了Arp2/3复合物和WASP家族蛋白的作用。在NIH 3T3细胞中,我们发现肌动蛋白和Arp2/3复合物有助于细胞极性的建立。此外,Scar2的N端片段(而非N-WASP或Scar1或Scar3)的过表达会干扰NIH 3T3高尔基体极化,但不影响细胞迁移。相比之下,肌动蛋白、Arp2/3和WASP家族蛋白似乎未参与星形胶质细胞的高尔基体极化。因此,我们的结果表明高尔基体极性建立的需求具有细胞类型特异性。此外,在NIH 3T3细胞中,Scar2和Arp2/3复合物似乎参与了定向迁移过程中高尔基体极性的建立和维持。