Fhos encodes a Drosophila Formin‐Like Protein participating in autophagic programmed cell death

Abstract

Summary: Larval tissues undergo programmed cell death (PCD) during Drosophila metamorphosis. PCD is triggered in a stage and tissue-specific fashion in response to ecdysone pulses. The understanding of how ecdysone induces the stage and tissue-specificity of cell death remains obscure. Several steroid-regulated primary response genes have been shown to act as key regulators of cellular responses to ecdysone by inducing a cascade of transcriptional regulation of late responsive genes. In this article, the authors identify Fhos as a gene that is required for Drosophila larval salivary gland destruction. Animals with a P-element mutation in Fhos possess persistent larval salivary glands, and precise excisions of this P-element insertion resulted in reversion of this salivary gland mutant phenotype. Fhos encodes the Drosophila homolog of mammalian Formin Fhos. Fhos is differentially transcribed during development and responds to ecdysone in a method that is similar to other cell death genes. Similarly to what has been shown for its mammalian counterpart, FHOS protein is translocated to the nucleus at later stages of cell death. Fhos mutants posses disrupted actin cytoskeleton dynamics in persistent salivary glands. Together, our data indicate that Fhos is a new ecdysone-regulated gene that is crucial for changes in the actin cytoskeleton during salivary gland elimination in Drosophila. genesis 50:672-684, 2012. V V C 2012 Wiley Periodicals, Inc.

The Drosophila FHOD1-like formin Knittrig acts through Rok to promote stress fiber formation and directed macrophage migration during the cellular immune response

“…The shortest isoform, Knittrig PB , lacks the C-terminal DAD and hence constitutes a constitutively active protein. The expression of this active isoform seems to be upregulated in pupal salivary glands during ecdysone-induced programmed cell death (Anhezini et al, 2012). Thus, uncontrolled, massive induction of F-actin might be an efficient way to induce apoptosis or to extrude single cells from the epithelium, as proposed previously (Farhadifar et al, 2007).…”

“…The developmental functions as well as the formin activity of Drosophila FHOD have not been addressed. However, recent microarray analyses revealed that the only member of the FHOD family in Drosophila becomes highly upregulated upon bacterial infection and in autophagic programmed cell death during pupal metamorphosis (Anhezini et al, 2012;Johansson et al, 2005).…”

Ecdysone-mediated programmed cell death in Drosophila

“…For example, components of the ribosome (RpS5, RpL13A, RpL37, RpLP1), the sorting nexin-like gene SH3PX1, a formin-like protein Fhos, a predicted malate dehydrogenase Mdh2 and the transcription factor Sox14 (Anhezini et al, 2012, Chittaranjan et al, 2009, Ritter and Beckstead, 2010, Wang et al, 2010. Knockdown of sox14 in salivary gland results in reduced transcripts of rpr, dronc and E93 but not Br-C, however it is unknown whether Sox14 directly regulates their transcription and what position Sox14 sits in the ecdysone-mediated transcriptional cascade if it does at all (Chittaranjan et al, 2009).…”

DAAM Is Required for Thin Filament Formation and Sarcomerogenesis during Muscle Development in Drosophila

“…Lmod and the mammalian formin Fhod3 have both been implicated in actin assembly in vertebrate striated muscles [6], [7] but subsequent work concluded that they are unlikely to contribute to actin nucleation during the initial stages of myofibril assembly [8], [9], [10], [11]. In fruit flies, the genome harbors no clear Lmod ortholog, and genetic analysis of the Drosophila Fhod ortholog, Fhos, and other members of the formin family, such as Diaphanous, Cappuccino or Form3, revealed no clear role in muscle development [12], [13], [14], [15].…”