title: The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation.
abstract: The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, as one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation.
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hori
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
authors.forename: Agathe
authors.initials: A
authors.lastname: Morand
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
authors.forename: Chiho
authors.initials: C
authors.lastname: Ikebe
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
authors.forename: David
authors.initials: D
authors.lastname: Frith
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
authors.forename: Ambrosius P
authors.initials: AP
authors.lastname: Snijders
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. Electronic address: takashi-toda@hiroshima-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Toda
mesh_terms: D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D011506:Proteins; C000605616:SSX2IP protein, human; C433889:WRAP73 protein, human
keywords: Bipolar spindle; Centriolar satellites; Centriole; Centrosome; Fission yeast; Spindle pole body (SPB); Super resolution microscopy; WD repeats