The formation and closure of macropinocytic cups in a model system
The formation and closure of macropinocytic cups in a model system
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DOI：
10.1101/2022.10.07.511330
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发表时间：
2023-04
期刊：
影响因子：
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通讯作者：
Judith E. Lutton;Helena L. E. Coker;Peggy I. Paschke;C. Munn;J. King;T. Bretschneider;R. Kay
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文献类型：
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作者：
Judith E. Lutton;Helena L. E. Coker;Peggy I. Paschke;C. Munn;J. King;T. Bretschneider;R. Kay
巨胞饮作用是一种保守的内吞过程，其中细胞将培养基吸收成微米大小的囊泡。在网骨藻中，巨胞饮杯在质膜中的PIP 3结构域周围形成，并通过肌动蛋白聚合而延伸。使用晶格光片显微镜，我们描述了如何杯起源，支持的F-肌动蛋白支架和形状的肌动蛋白聚合环，周围PIP 3域创建。杯子是如何闭合的尚不清楚。我们找到两种方法：唇闭合，其中在唇处的肌动蛋白聚合被向内重定向;以及基底闭合，其中其拉伸杯，最终导致膜分层和囊泡密封。杯状结构随着肌动蛋白聚合的扩大波而生长，它穿过细胞表面，捕获新的膜。我们建议，当这些波失速时，杯子关闭。这个“停滞波”的假设是通过一个概念模型进行测试，其中肌动蛋白聚合和膜张力的相互作用的力量，重新创建我们的许多观察。
Macropinocytosis is a conserved endocytic process where cells take up medium into micron-sized vesicles. In Dictyostelium, macropinocytic cups form around domains of PIP3 in the plasma membrane and extend by actin polymerization. Using lattice light-sheet microscopy, we describe how cups originate, are supported by an F-actin scaffold and shaped by a ring of actin polymerization, created around PIP3 domains. How cups close is unknown. We find two ways: lip closure, where actin polymerization at the lip is re-directed inwards; and basal closure, where it stretches the cup, eventually causing membrane delamination and vesicle sealing. Cups grow as expanding waves of actin polymerization that travel across the cell surface, capturing new membrane. We propose that cups close when these waves stall. This ‘stalled wave’ hypothesis is tested through a conceptual model, where the interplay of forces from actin polymerization and membrane tension recreates many of our observations.