Journal
JOURNAL OF CELL BIOLOGY
Volume 220, Issue 7, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202007005
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Funding
- Medical Research Council [MR/K015931/1]
- North West Cancer Research Fund [CR847]
- Liverpool Cancer Research UK Centre
- University of Liverpool
- MRC [MR/K015931/1] Funding Source: UKRI
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In Drosophila, the deubiquitinating enzyme nonstop/USP22 plays a crucial role in controlling actin polarization and cell polarity determinant during collective cell migration. This study reveals a novel function of SAGA-independent nonstop/USP22 in cell migration, providing insights for further research in systems where USP22 is required for cell motility and invasion.
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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