Drosophila USP22/non-stop regulates the Hippo pathway to polarise the actin cytoskeleton during collective border cell migration

Polarisation of the actin cytoskeleton is vital for the collective migration of cells in vivo. During invasive border cell migration in Drosophila, actin polarisation is directly controlled by Hippo pathway components, which reside 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 non-stop/USP22 in the expression of Hippo pathway components expanded and merlin; loss of non-stop function consequently leads to a redistribution of F-actin and the polarity determinant Crumbs, loss of polarised actin protrusions and premature tumbling of the border cell cluster. Non-stop is a component of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional coactivator complex, but SAGA9s 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 non-stop/USP22 in Hippo-mediated collective cell migration, which may help guide studies in other systems where USP22 is necessary for cell motility and invasion.