Filamin Is Required for Ring Canal Assembly and Actin Organization during Drosophila Oogenesis

Abstract

The remodeling of the actin cytoskeleton is essential for cell migration, cell division, and cell morphogenesis. Actin-binding proteins play a pivotal role in reorganizing the actin cytoskeleton in response to signals exchanged between cells. In consequence, actin-binding proteins are increasingly a focus of investigations into effectors of cell signaling and the coordination of cellular behaviors within developmental processes. One of the first actin-binding proteins identified was filamin, or actin-binding protein 280 (ABP280). Filamin is required for cell migration (Cunningham et al. 1992), and mutations in human α-filamin (FLN1; Fox et al. 1998) are responsible for impaired migration of cerebral neurons and give rise to periventricular heterotopia, a disorder that leads to epilepsy and vascular disorders, as well as embryonic lethality. We report the identification and characterization of a mutation in Drosophila filamin, the homologue of human α-filamin. During oogenesis, filamin is concentrated in the ring canal structures that fortify arrested cleavage furrows and establish cytoplasmic bridges between cells of the germline. The major structural features common to other filamins are conserved in Drosophila filamin. Mutations in Drosophila filamin disrupt actin filament organization and compromise membrane integrity during oocyte development, resulting in female sterility. The genetic and molecular characterization of Drosophila filamin provides the first genetic model system for the analysis of filamin function and regulation during development.

The actin cross-linker Filamin/Cheerio mediates tumor malignancy downstream of JNK signaling

“…We show that in the EAD of third-instar larvae, Cher protein localizes primarily to the PE, a monolayer of polarized cells that lie between the CE and the basal membrane. Consistent with the absence of an externally visible eye phenotype in cher mutant flies (Li et al, 1999;Sokol and Cooley, 1999), loss of Cher from EAD clones had no obvious effect (supplementary material Fig. S3).…”

Roles of myosin phosphatase duringDrosophiladevelopment

“…The cleavage furrow is then stabilized and transformed into an early ring canal, which contains only an outer rim including the actin binding protein anillin (Field and Alberts, 1995), glycoprotein mucin-D (Kramerova and Kramerov, 1999), and phosphotyrosine proteins (Robinson et al, 1994). Then, filamin (cheerio) (Li et al, 1999;Sokol and Cooley, 1999), aducin-like protein hts-RC and filamentous actin are recruited to the ring canal to form an inner-rim (Robinson et al, 1994;Yue and Spradling, 1992). At the same time, phosphotyrosine proteins are also detected in the inner rim.…”

The role of actin bundling proteins in the assembly of filopodia in epithelial cells

“…Deletion or mutations in any one of these five proteins is associated with an abnormal phenotype ( Table 1). [116][117][118][119][120][121][122][123] A polarized distribution of two or more actin bundling proteins during cell motility is likewise documented. 124 It is clear from studies done with Dictyostelium that even simple organisms such as amoeba require a whole spectrum of actin-binding proteins to perform basic cellular functions.…”