Deeks Michael J, Kaloriti Despina, Davies Brendan, Malhó Rui, Hussey Patrick J
The Integrative Cell Biology Laboratory, School of Biological and Biomedical Sciences, University of Durham, South Road, Durham DH1 3LE, United Kingdom.
Curr Biol. 2004 Aug 10;14(15):1410-4. doi: 10.1016/j.cub.2004.06.065.
The dynamic nature of the eukaryotic actin cytoskeleton is essential for the locomotion of animal cells and the morphogenesis of plant and fungal cells. The F-actin nucleating/branching activity of the Arp2/3 complex is a key function for all of these processes. The SCAR/WAVE family represents a group of Arp2/3 activators that are associated with lamellipodia formation. A protein complex of PIR121, NAP1, ABI, and HSPC300 is required for SCAR regulation by cell signaling pathways, but the exact nature of this interaction is controversial and represents a continually evolving model. The mechanism originally proposed was of a SCAR trans repressing complex supported by evidence from in vitro experiments. This model was reinforced by genetic studies in the Drosophila central nervous system and Dictyostelium, where the knockout of certain SCAR-complex components leads to excessive SCAR-mediated actin polymerization. Conflicting data have steadily accumulated from animal tissue culture experiments suggesting that the complex activates rather than represses in vivo SCAR activity. Recent biochemical evidence supports the SCAR-complex activator model. Here, we show that genetic observations in Arabidopsis are compatible with an activation model and provide one potential mechanism for the regulation of the newly identified Arabidopsis Arp2/3 complex.
真核肌动蛋白细胞骨架的动态性质对于动物细胞的运动以及植物和真菌细胞的形态发生至关重要。Arp2/3复合物的F-肌动蛋白成核/分支活性是所有这些过程的关键功能。SCAR/WAVE家族代表了一组与片状伪足形成相关的Arp2/3激活剂。细胞信号通路对SCAR的调节需要PIR121、NAP1、ABI和HSPC300的蛋白质复合物,但这种相互作用的确切性质存在争议,并且代表了一个不断发展的模型。最初提出的机制是基于体外实验证据的SCAR反式抑制复合物。果蝇中枢神经系统和盘基网柄菌的遗传学研究强化了这一模型,在这些研究中,某些SCAR复合物成分的敲除会导致SCAR介导的肌动蛋白过度聚合。动物组织培养实验不断积累的相互矛盾的数据表明,该复合物在体内激活而非抑制SCAR活性。最近的生化证据支持SCAR复合物激活模型。在这里,我们表明拟南芥中的遗传学观察结果与激活模型相符,并为新鉴定的拟南芥Arp2/3复合物的调节提供了一种潜在机制。