title: Regulation of cofilin phosphorylation and asymmetry in collective cell migration during morphogenesis.
abstract: During Drosophila oogenesis, two actin dynamics regulators, cofilin and Rac, are required for the collective migration of a coherent cluster of cells called border cells. Cell culture data have shown that Rac and cofilin are both essential for lamellipodium formation, but Rac signaling results in phosphorylation and hence inactivation of cofilin. So it remains unclear whether cofilin phosphorylation plays a promoting or inhibitory role during cell migration. We show here that cofilin is required for F-actin turnover and lamellipodial protrusion in the border cells. Interestingly, reducing the dosage of cofilin by half or expressing a phospho-mimetic mutant form, S3E, partially rescues the migration and protrusion defects of Rac-deficient border cells. Moreover, cofilin exhibits moderate accumulation in border cells at the migratory front of the cluster, whereas phospho-cofilin has a robust and uniform distribution pattern in all the outer border cells. Blocking or overactivating Rac signaling in border cells greatly reduces or increases cofilin phosphorylation, respectively, and each abolishes cell migration. Furthermore, Rac may signal through Pak and LIMK to result in uniform phosphorylation of cofilin in all the outer border cells, whereas the guidance receptor Pvr (PDGF/VEGF receptor) mediates the asymmetric localization of cofilin in the cluster but does not affect its phosphorylation. Our study provides one of the first models of how cofilin functions and is regulated in the collective migration of a group of cells in vivo.
authors.affiliation: Model Animal Research Center, and MOE Key Laboratory of Model Animals for Disease Study, Nanjing University, Nanjing, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.forename: Ping
authors.initials: P
authors.lastname: Wan
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Frank
authors.initials: F
authors.lastname: Laski
authors.forename: Jiong
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011554:Pseudopodia / Q000378:metabolism / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D053778:Thiazolidines; C097180:tsr protein, Drosophila; C438368:Pvr protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; C099277:Pak protein, Drosophila; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins; C037067:latrunculin A