Mendoza Michelle C, Vilela Marco, Juarez Jesus E, Blenis John, Danuser Gaudenz
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Departments of Cell and Tissue Biology and Pathology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Sci Signal. 2015 May 19;8(377):ra47. doi: 10.1126/scisignal.aaa8859.
Cells move through perpetual protrusion and retraction cycles at the leading edge. These cycles are coordinated with substrate adhesion and retraction of the cell rear. We tracked spatial and temporal fluctuations in the molecular activities of individual moving cells to elucidate how extracellular signal-regulated kinase (ERK) signaling controlled the dynamics of protrusion and retraction cycles. ERK is activated by many cell surface receptors, and we found that ERK signaling specifically reinforced cellular protrusions so that they translated into rapid, sustained forward motion of the leading edge. Using quantitative fluorescent speckle microscopy and cross-correlation analysis, we showed that ERK controlled the rate and timing of actin polymerization by promoting the recruitment of the actin nucleator Arp2/3 to the leading edge. These findings support a model in which surges in ERK activity induced by extracellular cues enhance Arp2/3-mediated actin polymerization to generate protrusion power phases with enough force to counteract increasing membrane tension and to promote sustained motility.
细胞在前缘通过持续的突起和回缩循环移动。这些循环与底物粘附以及细胞尾部的回缩相协调。我们追踪了单个移动细胞分子活动的时空波动，以阐明细胞外信号调节激酶（ERK）信号如何控制突起和回缩循环的动力学。ERK被许多细胞表面受体激活，我们发现ERK信号特异性地增强了细胞突起，从而使其转化为前缘快速、持续的向前运动。通过定量荧光斑点显微镜和互相关分析，我们表明ERK通过促进肌动蛋白成核剂Arp2/3向前缘的募集来控制肌动蛋白聚合的速率和时间。这些发现支持了一个模型，即细胞外信号诱导的ERK活性激增增强了Arp2/3介导的肌动蛋白聚合，以产生具有足够力量的突起动力阶段，以抵消不断增加的膜张力并促进持续的运动性。
