Drosophila USP22/nonstop polarizes the actin cytoskeleton during collective border cell migration.

Drosophila USP22/nonstop polarizes the actin cytoskeleton during collective border cell migration.
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果蝇USP 22/nonstop在集体边界细胞迁移期间极化肌动蛋白细胞骨架。

DOI:
10.1083/jcb.202007005
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发表时间:
2021-07-05
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Bennett D
Bennett D
中科院分区:
其他
文献类型:
--
作者:
Badmos H;Cobbe N;Campbell A;Jackson R;Bennett D

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Badmos等人。发现去泛素酶NONSTOP/USP22对于果蝇边缘细胞的集体迁移是必不可少的。在此背景下,NONSTOP调节河马信号通路组件的表达,极性决定因素的定位,以及肌动蛋白细胞骨架的极化。肌动蛋白细胞骨架的极化对于体内细胞的集体迁移是至关重要的。在果蝇侵袭性边缘细胞迁移过程中,肌动蛋白的极化直接由河马信号复合体控制,河马信号复合体位于簇中边缘细胞之间的接触处。在这里,我们在参与边界细胞迁移的去泛素化酶的遗传筛查中发现,NONSTOP/USP22在河马途径组分Expanded和Merlin的表达中发挥了重要作用。因此,失去不间断功能会导致F-肌动蛋白和极性决定簇的重新分布,极化肌动蛋白突起的丢失,以及边界细胞团的翻滚。NONSTOP是SPT-Ada-Gcn5-乙酰转移酶(SAGA)转录共激活复合体的组成部分,但SAGA的组蛋白乙酰转移酶模块不与Expand或Merlin结合,对于迁移是必不可少的。综上所述,我们的结果揭示了SAGA非依赖的NONSTOP/USP22在细胞集体迁移中的新角色,这可能有助于指导在其他系统中的研究,其中USP22是细胞运动和侵袭所必需的。
Badmos et al. find that the deubiquitinating enzyme nonstop/USP22 is essential for collective migration of Drosophila border cells. In this context, nonstop regulates the expression of hippo signaling pathway components, localization of polarity determinants, and polarization of the actin cytoskeleton. Polarization of the actin cytoskeleton is vital for the collective migration of cells in vivo. During invasive border cell migration in Drosophila, actin polarization is directly controlled by the Hippo signaling complex, which resides at contacts between border cells in the cluster. Here, we identify, in a genetic screen for deubiquitinating enzymes involved in border cell migration, an essential role for nonstop/USP22 in the expression of Hippo pathway components expanded and merlin. Loss of nonstop function consequently leads to a redistribution of F-actin and the polarity determinant Crumbs, loss of polarized actin protrusions, and tumbling of the border cell cluster. Nonstop is a component of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional coactivator complex, but SAGA’s histone acetyltransferase module, which does not bind to expanded or merlin, is dispensable for migration. Taken together, our results uncover novel roles for SAGA-independent nonstop/USP22 in collective cell migration, which may help guide studies in other systems where USP22 is necessary for cell motility and invasion.
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