Cofilin/ADF is required for cell motility during Drosophila ovary development and oogenesis

Abstract

The driving force behind cell motility is the actin cytoskeleton. Filopodia and lamellipodia are formed by the polymerization and extension of actin filaments towards the cell membrane. This polymerization at the barbed end of the filament is balanced by depolymerization at the pointed end, recycling the actin in a 'treadmilling' process. One protein involved in this process is cofilin/actin-depolymerizing factor (ADF), which can depolymerize actin filaments, allowing treadmilling to occur at an accelerated rate. Cofilin/ADF is an actin-binding protein that is required for actin-filament disassembly, cytokinesis and the organization of muscle actin filaments. There is also evidence that cofilin/ADF enhances cell motility, although a direct requirement in vivo has not yet been shown. Here we show that Drosophila cofilin/ADF, which is encoded by the twinstar (tsr) gene, promotes cell movements during ovary development and oogenesis. During larval development, cofilin/ADF is required for the cell rearrangement needed for formation of terminal filaments, stacks of somatic cells that are important for the initiation of ovarioles. It is also required for the migration of border cells during oogenesis. These results show that cofilin/ADF is an important regulator of actin-based cell motility during Drosophila development.

Actin-depolymerizing Factor and Cofilin-1 Play Overlapping Roles in Promoting Rapid F-Actin Depolymerization in Mammalian Nonmuscle Cells

“…These results are in accordance with previous data obtained with yeast, Drosophila, and C. elegans strains carrying mutations in ADF/cofilins as well as with studies in which ADF/cofilins were inactivated in cells by overexpression of LIM-kinase or by depletion of cyclase-associated protein, which is an important ADF/cofilin recycling protein in cells (Gunsalus et al, 1995;Lappalainen and Drubin, 1997;Arber et al, 1998;Yang et al, 1998;Ono et al, 1999;Chen et al, 2001;Dong et al, 2001;Niwa et al, 2002;Bertling et al, 2004). In contrast to these data, recent studies on EGF-stimulated rat adenocarcinoma cells indicated that instead of promoting filament depolymerization, ADF/cofilins would contribute to cytoskeletal dynamics by increasing the number of assembly competent barbed ends through their filament-severing activity.…”

“…Studies on the motility of Listeria and analysis of loss-of-function cofilin mutants in yeast indicated that ADF/cofilins enhance actin dynamics by depolymerizing actin filaments and provide actin monomers to the cytoplasmic pool (Carlier et al, 1997;Rosenblatt et al, 1997;Lappalainen and Drubin, 1997). Furthermore, cytoplasmic actin filaments accumulate when ADF/cofilins are mutated in Drosophila or Caenorhabditis elegans or when ADF/cofilins are inactivated by overexpressing LIM kinase (Gunsalus et al, 1995;Arber et al, 1998;Yang et al, 1998;Ono et al, 1999;Chen et al, 2001). In contrast, studies on epidermal growth factor (EGF)-stimulated rat mammary adenocarcinoma cells suggested that ADF/cofilin's biological role is to increase actin filament nucleation by severing actin filaments and thus create new filament barbed ends for actin assembly (Chan et al, 2000;Zebda et al, 2000;Ichetovkin et al, 2002;Ghosh et al, 2004).…”

The cofilin pathway in breast cancer invasion and metastasis

“…In lower eukaryotes such as Caenorhabditis elegans, different isoforms of cofilin are required for distinct steps in morphogenesis, including blastocyst positioning and body wall formation 57 . In Drosophila embryos, cofilin is required for cell migration during ovary development and oogenesis 58 , as well as in maintaining planar cell polarity in the wing, eye, and other epithelia 59 . Furthermore, flies that harbour mutations in genes that encode proteins involved in regulating cofilin phosphorylation provide further evidence for the role of the cofilin pathway in the regulation of Drosophila morphogenesis (BOX 2).…”

“…During Drosophila morphogenesis, the disruption of cofilin alleles by transposon mutagenesis caused an abnormal actin cytoskeleton characterized by large F-actin aggregates in primary spermatocytes and at the contractile ring during cytokinesis 92 , as well as the follicular epithelium during ovarian development 58 . Loss-of-function mutations in genes that regulate cofilin phosphorylation, such as the cofilin phosphatase slingshot and the cofilin kinase LIM kinase (LIMK), further support a role for cofilin in regulating actin dynamics during Drosophila morphogenesis.…”

The flare Gene, Which Encodes the AIP1 Protein of Drosophila, Functions to Regulate F-Actin Disassembly in Pupal Epidermal Cells

“…The twinstar (tsr) gene encodes the Drosophila cofilin (Gunsalus et al 1995). Mutations in this gene are also known to result in increased levels of F-actin in cells (Baum et al 2000) and surviving tsr hypomorphs 1 display abnormal bristles (Chen et al 2001;Wahlstrom et al 2001). tsr is essential at both the organismal and cell levels.…”