Reference - Detail
| RRC ID | 89821 |
|---|---|
| Author | Molitor D, Schillers H, Bogdan S. |
| Title | Cdc42 and Rac2 act through the formin-like Frl/FMNL to control lamellocyte shape and encapsulation of parasitoid wasp eggs in Drosophila. |
| Journal | PLoS Pathog |
| Abstract |
Drosophila has been established as a powerful genetic model to study not only blood cell development but also innate cellular immunity. Lamellocytes are the most distinct blood cell type which are large key effector cells in the anti-parasitoid immune response in Drosophila. Findings on cell morphology and function of lamellocytes are based on pioneering studies conducted in the early 1980s. Here, we analyzed their remarkable cell cytoskeleton and cell morphology using high-resolution microscopy combined with a lamellocyte-specific candidate RNAi approach to identify key regulators of the lamellocyte morphology and functions. Similar to disc-shaped rigid platelets in our bloodstream, non-migratory lamellocytes only passively circulate in the hemolymph. Once attached to parasitic wasp egg, lamellocytes undergo a marked reorganization of their cortical actin cytoskeleton promoting cell spreading and encapsulation of parasitic wasp eggs. Atomic force microscopy (AFM) indeed showed that lamellocytes become significantly softer while the cortical actin cytoskeleton reorganizes and forms lamellipodia-like protrusions to spread. Cortical actin cytoskeleton reorganization does not depend on WAVE-Arp2/3-branched actin filament nucleation but rather requires the formin Frl (also known as FMNL) downstream of Rac2 and Cdc42 signaling. Supporting this notion, RNAi-mediated depletion of either Frl/FMNL or Rac2 and Cdc42 but not Rac1 results in prominent changes in lamellocyte morphology and immune dysfunction. Our data further suggest a pathway in which Rac2/Cdc42 recruits Frl/FMNL to the cell cortex controlling lamellocyte spreading and encapsulation of parasitoid wasps. |
| Volume | 22(7) |
| Pages | e1014440 |
| Published | 2026-7-1 |
| DOI | 10.1371/journal.ppat.1014440 |
| PII | PPATHOGENS-D-25-03187 |
| PMID | 42475418 |
| PMC | PMC13395357 |
| MeSH | Animals Cell Shape Drosophila Proteins* / genetics Drosophila Proteins* / immunology Drosophila Proteins* / metabolism Drosophila melanogaster* / immunology Drosophila melanogaster* / parasitology Female Hemocytes* / immunology Hemocytes* / metabolism Microfilament Proteins* / metabolism Ovum / immunology RAC2 GTP-Binding Protein RNA Interference Wasps* / immunology cdc42 GTP-Binding Protein* / genetics cdc42 GTP-Binding Protein* / immunology cdc42 GTP-Binding Protein* / metabolism rac GTP-Binding Proteins* / genetics rac GTP-Binding Proteins* / immunology rac GTP-Binding Proteins* / metabolism |
| Resource | |
| Drosophila | 8556R-3 4636R-1 4636R-2 |