| RRC ID |
83337
|
| Author |
Rötte M, Höhne MY, Klug D, Ramlow K, Zedler C, Lehne F, Schneider M, Bischoff MC, Bogdan S.
|
| Title |
CYRI controls epidermal wound closure and cohesion of invasive border cell cluster in Drosophila.
|
| Journal |
J Cell Biol
|
| Abstract |
Cell motility is crucial for many biological processes including morphogenesis, wound healing, and cancer invasion. The WAVE regulatory complex (WRC) is a central Arp2/3 regulator driving cell motility downstream of activation by Rac GTPase. CYFIP-related Rac1 interactor (CYRI) proteins are thought to compete with WRC for interaction with Rac1 in a feedback loop regulating lamellipodia dynamics. However, the physiological role of CYRI proteins in vivo in healthy tissues is unclear. Here, we used Drosophila as a model system to study CYRI function at the cellular and organismal levels. We found that CYRI is not only a potent WRC regulator in single macrophages that controls lamellipodial spreading but also identified CYRI as a molecular brake on the Rac-WRC-Arp2/3 pathway to slow down epidermal wound healing. In addition, we found that CYRI limits invasive border cell migration by controlling cluster cohesion and migration. Thus, our data highlight CYRI as an important regulator of cellular and epithelial tissue dynamics conserved across species.
|
| Volume |
223(12)
|
| Published |
2024-12-2
|
| DOI |
10.1083/jcb.202310153
|
| PII |
277044
|
| PMID |
39453414
|
| PMC |
PMC11519390
|
| MeSH |
Actin-Related Protein 2-3 Complex / genetics
Actin-Related Protein 2-3 Complex / metabolism
Animals
Cell Movement*
Drosophila Proteins* / genetics
Drosophila Proteins* / metabolism
Drosophila melanogaster* / genetics
Drosophila melanogaster* / metabolism
Epidermis* / metabolism
Epidermis* / pathology
Macrophages / metabolism
Pseudopodia* / metabolism
Signal Transduction
Wound Healing*
rac GTP-Binding Proteins / genetics
rac GTP-Binding Proteins / metabolism
|
| IF |
8.811
|
| Resource |
| Drosophila |
4636R-1 |