Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
Dev Cell. 2019 Apr 22;49(2):189-205.e6. doi: 10.1016/j.devcel.2019.03.025.
Efficient chemotaxis requires rapid coordination between different parts of the cell in response to changing directional cues. Here, we investigate the mechanism of front-rear coordination in chemotactic neutrophils. We find that changes in the protrusion rate at the cell front are instantaneously coupled to changes in retraction at the cell rear, while myosin II accumulation at the rear exhibits a reproducible 9-15-s lag. In turning cells, myosin II exhibits dynamic side-to-side relocalization at the cell rear in response to turning of the leading edge and facilitates efficient turning by rapidly re-orienting the rear. These manifestations of front-rear coupling can be explained by a simple quantitative model incorporating reversible actin-myosin interactions with a rearward-flowing actin network. Finally, the system can be tuned by the degree of myosin regulatory light chain (MRLC) phosphorylation, which appears to be set in an optimal range to balance persistence of movement and turning ability.
高效的趋化性需要细胞的不同部分在响应不断变化的定向信号时迅速协调。在这里，我们研究了趋化性中性粒细胞中前后协调的机制。我们发现，细胞前端的突起速度变化与细胞后端的回缩变化瞬时耦合，而肌球蛋白 II 在后端的积累则表现出可重复的 9-15 秒延迟。在转弯的细胞中，肌球蛋白 II 在细胞后端表现出动态的侧向再定位，以响应前缘的转弯，并通过快速重新定向后端来促进有效的转弯。这种前后耦合的表现可以通过一个简单的定量模型来解释，该模型将可逆的肌动球蛋白相互作用与向后流动的肌动球蛋白网络结合在一起。最后，该系统可以通过肌球蛋白调节轻链（MRLC）磷酸化的程度进行调节，这似乎被设定在一个最佳范围内，以平衡运动的持久性和转弯能力。
