The BTB protein MEL-26 promotes cytokinesis in C. elegans by a CUL-3-independent mechanism.
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.
Luke-Glaser
Sarah
S
Institute of Biochemistry, HPM G 8.0, ETH Hönggerberg, 8093 Zürich, Switzerland.
Pintard
Lionel
L
Lu
Chenggang
C
Mains
Paul E
PE
Peter
Matthias
M
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
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