Cell migration is driven by pushing and pulling activities of the actin cytoskeleton, but migration directionality is largely controlled by microtubules. This function of microtubules is especially critical for neuron navigation. However, the underlying mechanisms are poorly understood. Here we show that branched actin filament networks, the main pushing machinery in cells, grow directly from microtubule tips toward the leading edge in growth cones of hippocampal neurons. Adenomatous polyposis coli (APC), a protein with both tumor suppressor and cytoskeletal functions, concentrates at the microtubule-branched network interface, whereas APC knockdown nearly eliminates branched actin in growth cones and prevents growth cone recovery after repellent-induced collapse. Conversely, encounters of dynamic APC-positive microtubule tips with the cell edge induce local actin-rich protrusions. Together, we reveal a novel mechanism of cell navigation involving APC-dependent assembly of branched actin networks on microtubule tips.

中文翻译：

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腺瘤性息肉病大肠杆菌将分支肌动蛋白网络组装在微管上，用于靶向膜突出

细胞迁移是由肌动蛋白细胞骨架的推拉活动驱动的，但迁移方向很大程度上由微管控制。微管的这种功能对于神经元导航尤其重要。然而，人们对潜在机制知之甚少。在这里，我们展示了分支肌动蛋白丝网络，细胞中的主要推动机制，直接从微管尖端向海马神经元生长锥的前缘生长。腺瘤性结肠息肉病 (APC) 是一种兼具肿瘤抑制和细胞骨架功能的蛋白质，集中在微管分支网络界面，而 APC 敲低几乎消除了生长锥中的分支肌动蛋白，并阻止生长锥在驱避剂诱导的崩溃后恢复。相反，动态 APC 阳性微管尖端与细胞边缘的相遇会诱导局部富含肌动蛋白的突起。我们共同揭示了一种新的细胞导航机制，涉及微管尖端上分支肌动蛋白网络的 APC 依赖性组装。