Vitriol Eric A, McMillen Laura M, Kapustina Maryna, Gomez Shawn M, Vavylonis Dimitrios, Zheng James Q
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Department of Physics, Lehigh University, Bethlehem, PA 18015, USA.
Cell Rep. 2015 Apr 21;11(3):433-45. doi: 10.1016/j.celrep.2015.03.033. Epub 2015 Apr 10.
Lamellipodia, the sheet-like protrusions of motile cells, consist of networks of actin filaments (F-actin) regulated by the ordered assembly from and disassembly into actin monomers (G-actin). Traditionally, G-actin is thought to exist as a homogeneous pool. Here, we show that there are two functionally and molecularly distinct sources of G-actin that supply lamellipodial actin networks. G-actin originating from the cytosolic pool requires the monomer-binding protein thymosin β4 (Tβ4) for optimal leading-edge localization, is targeted to formins, and is responsible for creating an elevated G/F-actin ratio that promotes membrane protrusion. The second source of G-actin comes from recycled lamellipodia F-actin. Recycling occurs independently of Tβ4 and appears to regulate lamellipodia homeostasis. Tβ4-bound G-actin specifically localizes to the leading edge because it does not interact with Arp2/3-mediated polymerization sites found throughout the lamellipodia. These findings demonstrate that actin networks can be constructed from multiple sources of monomers with discrete spatiotemporal functions.
板状伪足是运动细胞的片状突起，由肌动蛋白丝（F-肌动蛋白）网络组成，该网络由肌动蛋白单体（G-肌动蛋白）的有序组装和解聚所调控。传统上，G-肌动蛋白被认为是以均匀的池状形式存在。在此，我们表明存在两种功能和分子层面不同的G-肌动蛋白来源，它们为板状伪足的肌动蛋白网络提供物质。源自胞质池的G-肌动蛋白需要单体结合蛋白胸腺素β4（Tβ4）以实现最佳的前沿定位，靶向formin蛋白，并负责产生升高的G/F-肌动蛋白比率，从而促进膜的突出。G-肌动蛋白的第二个来源来自循环利用的板状伪足F-肌动蛋白。循环利用独立于Tβ4发生，并且似乎调节板状伪足的稳态。与Tβ4结合的G-肌动蛋白特异性定位于前沿，因为它不与遍布板状伪足的Arp2/3介导的聚合位点相互作用。这些发现表明，肌动蛋白网络可以由具有离散时空功能的多种单体来源构建而成。
