The Mother Centriole Appendage Protein Cenexin Modulates Lumen Formation through Spindle Orientation
Program in Molecular Medicine
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.
DOI of Published Version
Curr Biol. 2016 Mar 21;26(6):793-801. doi: 10.1016/j.cub.2016.01.025. Epub 2016 Mar 3. Link to article on publisher's site
Current biology : CB
Hung, Hui-Fan; Hehnly, Heidi; and Doxsey, Stephen J., "The Mother Centriole Appendage Protein Cenexin Modulates Lumen Formation through Spindle Orientation" (2016). Program in Molecular Medicine Publications and Presentations. 45.