Twinstar/cofilin is required for regulation of epithelial integrity and tissue growth in Drosophila

Cited 6 time in webofscience Cited 0 time in scopus
  • Hit : 434
  • Download : 0
Regulation of actin assembly and depolymerization is important for the organization of epithelia. Recent studies have shown that the actin-capping proteins are required to prevent cell extrusion and inappropriate activation of Yorkie (Yki) activity in Drosophila, implicating the importance of actin regulation for epithelial integrity and Yki-dependent tissue growth. However, the role of Twinstar (Tsr), the Drosophila homolog for cofilin/actin depolymerization factor (ADF), in epithelial integrity and Hippo signaling is unknown. Here we demonstrate that reduction of Tsr by RNA interference (RNAi) or mutant clones in wing imaginal disc induces not only F-actin accumulation but also ectopic expression of Wingless (Wg) and Yki target gene expanded (ex). Knockdown of Yki in Tsr-depleted cells reduced the level of ectopic Wg expression. Reduced Tsr also led to downregulation of cell junction proteins and extrusion of affected cells from the basal part of the epithelium. Rho GTPase 1 was upregulated in Tsr-depleted tissue, supporting the Tsr function in the inhibition of cell extrusion from the epithelium. Tsr is also required for blocking cell death and c-Jun N-terminal kinase (JNK) signaling. Ectopic JNK activation induced caspase activation but did not cause cell extrusion. Further, the invasiveness of Tsr-depleted cells was not suppressed by inhibition of cell death or JNK signaling. In contrast, Yki upregulation was significantly suppressed by cell death inhibition. Taken together, our data suggest that Tsr is required for cell survival and tissue growth by regulating JNK and Yki signaling while maintaining the epithelial integrity by controlling cell junctions. This study provides an insight into potential roles of ADF/cofilin in invasive cell migration and tumor suppression in higher animals.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2016-09
Language
English
Article Type
Article
Keywords

ACTIN-CAPPING-PROTEIN; HIPPO PATHWAY; CELL POLARITY; F-ACTIN; SIGNALING PATHWAYS; COFILIN; APOPTOSIS; SLINGSHOT; MIGRATION; PROLIFERATION

Citation

ONCOGENE, v.35, no.39, pp.5144 - 5154

ISSN
0950-9232
DOI
10.1038/onc.2016.46
URI
http://hdl.handle.net/10203/213890
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 6 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0