The core autophagy protein ATG9A controls dynamics of cell protrusions and directed migration.
The core autophagy protein ATG9A controls dynamics of cell protrusions and directed migration.
复制标题
核心自噬蛋白ATG9A控制细胞突起和定向迁移的动力学。
DOI：
10.1083/jcb.202106014
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发表时间：
2022-03-07
期刊：
影响因子：
--
通讯作者：
Morin F
中科院分区：
文献类型：
--
作者：
Campisi D;Desrues L;Dembélé KP;Mutel A;Parment R;Gandolfo P;Castel H;Morin F
Campisi等人通过证明ATG 9A阳性囊泡在趋化刺激期间被动员以参与前缘突起的延伸和稳定，揭示了核心自噬蛋白ATG 9A在细胞迁移中的新功能。趋化性迁移是一种基本的细胞行为，依赖于脂质和货物蛋白向前沿的协调流动。我们发现核心自噬蛋白ATG 9A在几种人类细胞系的趋化迁移中起着关键作用，包括高度侵袭性的神经胶质瘤细胞。消耗ATG 9A蛋白改变了形成大的和持久的丝状肌动蛋白（F-肌动蛋白）丰富的片状伪足，通常驱动定向迁移。使用活细胞TIRF显微镜，我们证明了ATG 9A阳性囊泡的目标是朝向极化细胞的迁移前沿，在那里它们的胞吐作用与扩散活性相关。最后，我们发现ATG 9A对于将β1整合素有效递送至前沿和正常粘附动力学至关重要。总的来说，我们的数据揭示了ATG 9A蛋白的新功能，并表明ATG 9A阳性囊泡在趋化刺激过程中被动员，以促进板状伪足的扩张及其锚定到细胞外基质。
Campisi et al. uncover a new function of the core autophagy protein ATG9A in cell migration by demonstrating that ATG9A-positive vesicles are mobilized during chemotactic stimulation to participate in the extension and stabilization of leading-edge protrusions. Chemotactic migration is a fundamental cellular behavior relying on the coordinated flux of lipids and cargo proteins toward the leading edge. We found here that the core autophagy protein ATG9A plays a critical role in the chemotactic migration of several human cell lines, including highly invasive glioma cells. Depletion of ATG9A protein altered the formation of large and persistent filamentous actin (F-actin)–rich lamellipodia that normally drive directional migration. Using live-cell TIRF microscopy, we demonstrated that ATG9A-positive vesicles are targeted toward the migration front of polarized cells, where their exocytosis correlates with protrusive activity. Finally, we found that ATG9A was critical for efficient delivery of β1 integrin to the leading edge and normal adhesion dynamics. Collectively, our data uncover a new function for ATG9A protein and indicate that ATG9A-positive vesicles are mobilized during chemotactic stimulation to facilitate expansion of the lamellipodium and its anchorage to the extracellular matrix.
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