Phagocytic 'teeth' and myosin-II 'jaw' power target constriction during phagocytosis.
Phagocytic 'teeth' and myosin-II 'jaw' power target constriction during phagocytosis.
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DOI：
10.7554/elife.68627
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发表时间：
2021-10-28
期刊：
影响因子：
7.7
通讯作者：
Krendel M
中科院分区：
文献类型：
--
作者：
Vorselen D;Barger SR;Wang Y;Cai W;Theriot JA;Gauthier NC;Krendel M
吞噬作用需要快速的肌动蛋白重组和空间控制力的产生，以摄取从病原体到凋亡细胞的目标。肌动球蛋白的活性如何指导膜扩展以吞噬如此多样的目标仍不清楚。在这里，我们结合了晶格光片显微镜（LLSM）和微粒牵引力显微镜（MP-TFM）来量化巨噬细胞吞噬过程中的肌动蛋白动力学和亚细胞力。我们发现，导致目标收缩的空间局部力在抗体活化的目标吞噬过程中是突出的。这种收缩主要是由arp2 /3介导的含有肌球蛋白1e和1f（“牙齿”）的离散肌动蛋白突起的组装驱动的，这些肌动蛋白突起在环状组织中相互连接。收缩肌球蛋白ii活性有助于后期吞噬力的产生和进展，支持吞噬杯闭合的特定作用。对部分目标进食尝试和突发性目标释放机制的观察表明，收缩可能对解决复杂的体内目标遭遇至关重要。总的来说，我们的研究结果表明，吞噬杯形机制不同于二维细胞运动中的细胞骨架重塑，可能有助于机械感知和吞噬可塑性。
Phagocytosis requires rapid actin reorganization and spatially controlled force generation to ingest targets ranging from pathogens to apoptotic cells. How actomyosin activity directs membrane extensions to engulf such diverse targets remains unclear. Here, we combine lattice light-sheet microscopy (LLSM) with microparticle traction force microscopy (MP-TFM) to quantify actin dynamics and subcellular forces during macrophage phagocytosis. We show that spatially localized forces leading to target constriction are prominent during phagocytosis of antibody-opsonized targets. This constriction is largely driven by Arp2/3-mediated assembly of discrete actin protrusions containing myosin 1e and 1f (‘teeth’) that appear to be interconnected in a ring-like organization. Contractile myosin-II activity contributes to late-stage phagocytic force generation and progression, supporting a specific role in phagocytic cup closure. Observations of partial target eating attempts and sudden target release via a popping mechanism suggest that constriction may be critical for resolving complex in vivo target encounters. Overall, our findings present a phagocytic cup shaping mechanism that is distinct from cytoskeletal remodeling in 2D cell motility and may contribute to mechanosensing and phagocytic plasticity.