title: Actin Cytoskeletal Organization in Drosophila Germline Ring Canals Depends on Kelch Function in a Cullin-RING E3 Ligase.
abstract: The Drosophila Kelch protein is required to organize the ovarian ring canal cytoskeleton. Kelch binds and cross-links F-actin in vitro, and it also functions with Cullin 3 (Cul3) as a component of a ubiquitin E3 ligase. How these two activities contribute to cytoskeletal remodeling in vivo is not known. We used targeted mutagenesis to investigate the mechanism of Kelch function. We tested a model in which Cul3-dependent degradation of Kelch is required for its function, but we found no evidence to support this hypothesis. However, we found that mutant Kelch deficient in its ability to interact with Cul3 failed to rescue the kelch cytoskeletal defects, suggesting that ubiquitin ligase activity is the principal activity required in vivo. We also determined that the proteasome is required with Kelch to promote the ordered growth of the ring canal cytoskeleton. These results indicate that Kelch organizes the cytoskeleton in vivo by targeting a protein substrate for degradation by the proteasome.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hudson
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520.
authors.forename: Katelynn M
authors.initials: KM
authors.lastname: Mannix
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520 Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06510 lynn.cooley@yale.edu.
authors.forename: Lynn
authors.initials: L
authors.lastname: Cooley
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D044842:Cullin Proteins / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D004330:Drosophila / Q000033:anatomy & histology / Q000166:cytology; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D005836:Genitalia, Female / Q000166:cytology; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D016296:Mutagenesis; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*
chemical_list: D000199:Actins; C503647:Cul3 protein, Drosophila; D044842:Cullin Proteins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C080353:kel protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Drosophila; actin; cullin; oogenesis; proteasome