title: Neurl4, a novel daughter centriole protein, prevents formation of ectopic microtubule organizing centres.
abstract: Here we identify Neuralized homologue 4 (Neurl4) as a protein that interacts with CP110, a centrosomal protein that regulates centrosome duplication. Neurl4 uses a Neuralized homology repeat to preferentially localize to procentrioles and daughter centrioles. Neurl4 depletion results in ectopic microtubular organizing centres (MTOCs), leading to accumulation of CP110 and recruitment of a cohort of centrosomal proteins. We show that these ectopic MTOCs persist through mitosis and assemble aberrant mitotic spindles. Interestingly, Neurl4 promotes ubiquitylation of CP110, thereby destabilizing this protein. Our results indicate that Neurl4 counteracts accumulation of CP110, thereby maintaining normal centriolar homeostasis and preventing formation of ectopic MTOCs.
authors.affiliation: Department of Pathology, OCS Microscopy Core, New York University School of Medicine and Cancer Institute, 522 First Avenue, Smilow 1106, New York, New York 10016, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Sehyun
authors.initials: S
authors.lastname: Kim
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Feng-Xia
authors.initials: FX
authors.lastname: Liang
authors.forename: Nina
authors.initials: N
authors.lastname: Korzeniewski
authors.forename: Stefan
authors.initials: S
authors.lastname: Duensing
authors.forename: Brian D
authors.initials: BD
authors.lastname: Dynlacht
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism* / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000378:metabolism*; D008938:Mitosis; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D034622:RNA Interference; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
chemical_list: C467559:CCP110 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; C575176:Neurl4 protein, human; D044767:Ubiquitin-Protein Ligases