The tumor suppressor Lgl1 regulates front-rear polarity of migrating cells
The tumor suppressor Lgl1 regulates front-rear polarity of migrating cells
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DOI：
10.4161/cam.29387
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发表时间：
2014-07
影响因子：
3.2
通讯作者：
S. Ravid
中科院分区：
文献类型：
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作者：
S. Ravid
细胞迁移是一个高度整合的多步骤过程，在生理和病理过程中起着重要作用。迁移细胞是高度极化的，具有复杂的调节途径，在空间和时间上整合其组成过程。1果蝇肿瘤抑制因子Lethal（2）giant larvae（Lgl）调节上皮细胞的顶-底极性和不对称细胞分裂。2但关于Lgl在迁移细胞中建立细胞极性的作用知之甚少。最近，我们发现哺乳动物Lgl 1与非肌肉肌球蛋白IIA（NMIIA）直接相互作用，抑制其在体外组装成肌丝的能力。3 Lgl 1还调节NMIIA的细胞定位，粘着斑的成熟，我们进一步表明，aPKC β对Lgl 1的磷酸化阻止了它与NMIIA的相互作用，对Lgl 1和acto-1的相互作用非常重要。4 Lgl是Par 6-aPKC细胞极性复合物的关键下游靶标;我们发现Lgl 1在体内形成两种不同的复合物，Lgl 1-NMIIA和Lgl 1-Par 6-aPKC在不同的细胞区室中结合。4我们进一步发现aPKC β和NMIIA通过相同的结构域竞争直接结合Lgl 1。这些数据提供了新的见解Lgl 1，NMIIA，和Par 6-aPKC β在建立迁移细胞的前后极性的作用。在这篇评论中，我讨论的作用，LGL 1在调节的acto-NMII细胞骨架和其调节的Par 6-aPKC的极性复合物，以及如何LGL 1的活动可能有助于建立前-后极性迁移细胞。
Cell migration is a highly integrated, multistep process that plays an important role in physiological and pathological processes. The migrating cell is highly polarized, with complex regulatory pathways that integrate its component processes spatially and temporally.1 The Drosophila tumor suppressor, Lethal (2) giant larvae (Lgl), regulates apical-basal polarity in epithelia and asymmetric cell division.2 But little is known about the role of Lgl in establishing cell polarity in migrating cells. Recently, we showed that the mammalian Lgl1 interacts directly with non-muscle myosin IIA (NMIIA), inhibiting its ability to assemble into filaments in vitro.3 Lgl1 also regulates the cellular localization of NMIIA, the maturation of focal adhesions, and cell migration.3 We further showed that phosphorylation of Lgl1 by aPKCζ prevents its interaction with NMIIA and is important for Lgl1 and acto-NMII cytoskeleton cellular organization.4 Lgl is a critical downstream target of the Par6-aPKC cell polarity complex; we showed that Lgl1 forms two distinct complexes in vivo, Lgl1-NMIIA and Lgl1-Par6-aPKCζ in different cellular compartments.4 We further showed that aPKCζ and NMIIA compete to bind directly to Lgl1 through the same domain. These data provide new insights into the role of Lgl1, NMIIA, and Par6-aPKCζ in establishing front-rear polarity in migrating cells. In this commentary, I discuss the role of Lgl1 in the regulation of the acto-NMII cytoskeleton and its regulation by the Par6-aPKCζ polarity complex, and how Lgl1 activity may contribute to the establishment of front-rear polarity in migrating cells.