title: The Mother Centriole Appendage Protein Cenexin Modulates Lumen Formation through Spindle Orientation.
abstract: Establishing apical-basal polarity is instrumental in the functional shaping of a solitary lumen within an acinus. By exploiting micropatterned slides, wound healing assays, and three-dimensional culture systems, we identified a mother centriole subdistal appendage protein, cenexin, as a critical player in symmetric lumen expansion through the control of microtubule organization. In this regard, cenexin was required for both centrosome positioning in interphase cells and proper spindle orientation during mitosis. In contrast, the essential mother centriole distal appendage protein CEP164 did not play a role in either process, demonstrating the specificity of subdistal appendages for these events. Importantly, upon closer examination we found that cenexin depletion decreased astral microtubule length, disrupted astral microtubule minus-end organization, and increased levels of the polarity protein NuMA at the cell cortex. Interestingly, spindle misorientation and NuMA mislocalization were reversed by treatment with a low dose of the microtubule-stabilizing agent paclitaxel. Taken together, these results suggest that cenexin modulates microtubule organization and stability to mediate spindle orientation.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Hung
authors.affiliation: Department of Cell and Developmental Biology, State University of New York Upstate Medical School, Syracuse, NY 13210, USA. Electronic address: hehnlyh@upstate.edu.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hehnly
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: stephen.doxsey@umassmed.edu.
authors.forename: Stephen
authors.initials: S
authors.lastname: Doxsey
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D002465:Cell Movement; D002502:Centrioles / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; C524694:CEP164 protein, human; D018797:Cell Cycle Proteins; D006360:Heat-Shock Proteins; D008868:Microtubule Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; C490107:ODF2 protein, human; D015739:Nocodazole