title: The BTB protein MEL-26 promotes cytokinesis in C. elegans by a CUL-3-independent mechanism.
abstract: BACKGROUND
  The initiation of a cleavage furrow is essential to separate cells during cytokinesis, but little is known about the mechanisms controlling this actin-driven process. Previous studies in C. elegans embryos revealed that inactivation of the CUL-3-based E3 ligase activator rfl-1 results in an aberrant microtubule network, ectopic furrowing during pronuclear migration, and defects during cytokinesis.
  
  
  RESULTS
  Here, we show that MEL-26, a substrate-specific adaptor of the CUL-3-based E3 ligase, is required for efficient cell separation and cleavage furrow ingression during the C. elegans early mitotic divisions. Loss of MEL-26 function leads to delayed onset and slow ingression of cytokinesis furrows that frequently regress. Conversely, increased levels of MEL-26 in cul-3(RNAi) and rfl-1 mutant embryos cause a hypercontractile cortex, with several simultaneously ingressing furrows during pronuclear migration. MEL-26 accumulates at cleavage furrows and binds the actin-interacting protein POD-1. Importantly, POD-1 is not a substrate of the MEL-26/CUL-3 ligase but is required to localize MEL-26 to the cortex.
  
  
  CONCLUSIONS
  Our results suggest that MEL-26 not only acts as a substrate-specific adaptor within the MEL-26/CUL-3 complex, but also promotes cytokinesis by a CUL-3- and microtubule-independent mechanism.
authors.affiliation: Institute of Biochemistry, HPM G 8.0, ETH Hönggerberg, 8093 Zürich, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Luke-Glaser
authors.forename: Lionel
authors.initials: L
authors.lastname: Pintard
authors.forename: Chenggang
authors.initials: C
authors.lastname: Lu
authors.forename: Paul E
authors.initials: PE
authors.lastname: Mains
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D044842:Cullin Proteins / Q000235:genetics; D048749:Cytokinesis / Q000502:physiology*; D004926:Escherichia coli; D005822:Genetic Vectors; D005982:Glutathione Transferase; D015151:Immunoblotting; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000378:metabolism; D034622:RNA Interference; D012441:Saccharomyces cerevisiae
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D044842:Cullin Proteins; C114960:Mel-26 protein, C elegans; D008840:Microfilament Proteins; C401782:POD-1 protein, C elegans; D005982:Glutathione Transferase