Capping protein is essential for cell migration in vivo and for filopodial morphology and dynamics.
Capping protein is essential for cell migration in vivo and for filopodial morphology and dynamics.
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DOI：
10.1091/mbc.e13-12-0749
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发表时间：
2014-07-15
影响因子：
3.3
通讯作者：
Halpain S
中科院分区：
文献类型：
--
作者：
Sinnar SA;Antoku S;Saffin JM;Cooper JA;Halpain S
这项研究表明，加帽蛋白（CP）对于哺乳动物细胞的体外和体内迁移至关重要。作者还表明，CP 存在于多种细胞类型的丝状伪足中，并且它调节丝状伪足的结构和功能。因此，板状伪足和丝状伪足中的 CP 功能可能有助于有效迁移。加帽蛋白 (CP) 与正在生长的肌动蛋白丝的有倒刺的末端结合并抑制伸长。 CP 对于无细胞系统和盘基网柄菌中基于肌动蛋白的运动至关重要。尽管 CP 被认为对于形成突出和迁移所需的片状肌动蛋白结构至关重要，但 CP 在哺乳动物细胞迁移中的作用尚未得到直接测试。此外，最近的研究表明，除了片状伪足之外的结构，包括片层和丝状伪足，可能在细胞迁移中具有未被认识到的作用。 CP 被认为在丝状伪足中不存在，因此其在丝状伪足活动中的作用仍未被探索。我们报告说，在培养的哺乳动物 B16F10 细胞和发育中的新皮质神经元中沉默 CP 会损害细胞迁移。此外，我们出乎意料地观察到，在大多数丝状伪足中可检测到低水平的 CP。 CP耗尽减少了丝状伪足长度、改变了丝状伪足形状并降低了丝状伪足动力学。我们的结果通过将 CP 与丝状伪足和板状伪足联系起来，支持扩大 CP 在细胞运动中发挥的潜在作用，这两者对于许多类型的迁移细胞的运动都很重要。
This study shows that capping protein (CP) is essential for mammalian cell migration in vitro and in vivo. The authors also show that CP is present in filopodia of multiple cell types and that it regulates filopodial structure and function. Thus CP function in both lamellipodia and filopodia may contribute to efficient migration. Capping protein (CP) binds to barbed ends of growing actin filaments and inhibits elongation. CP is essential for actin-based motility in cell-free systems and in Dictyostelium. Even though CP is believed to be critical for creating the lamellipodial actin structure necessary for protrusion and migration, CP's role in mammalian cell migration has not been directly tested. Moreover, recent studies have suggested that structures besides lamellipodia, including lamella and filopodia, may have unappreciated roles in cell migration. CP has been postulated to be absent from filopodia, and thus its role in filopodial activity has remained unexplored. We report that silencing CP in both cultured mammalian B16F10 cells and in neurons of developing neocortex impaired cell migration. Moreover, we unexpectedly observed that low levels of CP were detectable in the majority of filopodia. CP depletion decreased filopodial length, altered filopodial shape, and reduced filopodial dynamics. Our results support an expansion of the potential roles that CP plays in cell motility by implicating CP in filopodia as well as in lamellipodia, both of which are important for locomotion in many types of migrating cells.