title: WD repeat-containing protein 5 (WDR5) localizes to the midbody and regulates abscission.
abstract: Cytokinesis partitions the cytoplasm of a parent cell into two daughter cells and is essential for the completion of cell division. The final step of cytokinesis in animal cells is abscission, which is a process leading to the physical separation of two daughter cells. Abscission requires membrane traffic and microtubule disassembly at a specific midbody region called the secondary ingression. Here, we report that WD repeat-containing protein 5 (WDR5), a core subunit of COMPASS/MLL family histone H3 lysine 4 methyltransferase (H3K4MT) complexes, resides at the midbody and associates with a subset of midbody regulatory proteins, including PRC1 and CYK4/MKLP1. Knockdown of WDR5 impairs abscission and increases the incidence of multinucleated cells. Further investigation revealed that the abscission delay is primarily due to slower formation of secondary ingressions in WDR5 knockdown cells. Consistent with these defects, midbody microtubules in WDR5 knockdown cells also display enhanced resistance to depolymerization by nocodazole. Recruitment of WDR5 to the midbody dark zone appears to require integrity of the WDR5 central arginine-binding cavity, as mutations that disrupt histone H3 and MLL1 binding to this pocket also abolish the midbody localization of WDR5. Taken together, these data suggest that WDR5 is specifically targeted to the midbody in the absence of chromatin and that it promotes abscission, perhaps by facilitating midbody microtubule disassembly.
authors: From the Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California at Santa Barbara, Santa Barbara, California 93106.
authors: Jeffrey K
authors: JK
authors: Bailey
authors: From the Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California at Santa Barbara, Santa Barbara, California 93106.
authors: Alexander T
authors: AT
authors: Fields
authors: From the Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California at Santa Barbara, Santa Barbara, California 93106.
authors: Kaijian
authors: K
authors: Cheng
authors: From the Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California at Santa Barbara, Santa Barbara, California 93106.
authors: Albert
authors: A
authors: Lee
authors: From the Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California at Santa Barbara, Santa Barbara, California 93106.
authors: Eric
authors: E
authors: Wagenaar
authors: From the Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California at Santa Barbara, Santa Barbara, California 93106.
authors: Remy
authors: R
authors: Lagrois
authors: From the Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California at Santa Barbara, Santa Barbara, California 93106.
authors: Bailey
authors: B
authors: Schmidt
authors: From the Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California at Santa Barbara, Santa Barbara, California 93106.
authors: Bin
authors: B
authors: Xia
authors: From the Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California at Santa Barbara, Santa Barbara, California 93106 ma@lifesci.ucsb.edu.
authors: Dzwokai
authors: D
authors: Ma
mesh_terms: D001483:Base Sequence; D016923:Cell Death; D017931:DNA Primers; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008856:Microscopy, Fluorescence
chemical_list: D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C502547:WDR5 protein, human; D011495:Histone-Lysine N-Methyltransferase
keywords: Abscission; Cell Division; Cytokinesis; H3K4; Histone Methylation; Microtubule; Molecular Cell Biology; Secondary Ingression; WDR5