TY - JOUR
T1 - The mother centriole appendage protein cenexin modulates lumen formation through spindle orientation
AU - Hung, Hui Fang
AU - Hehnly, Heidi
AU - Doxsey, Stephen
N1 - Funding Information:
We thank Christine Powers (UMMS) for assistance with EM processing and imaging, Joshua van Kleef and Yu-Shan Hung (ANU) for assistance with MATLAB software, and YoonJeung Chang and Wendy Zimmerman (UMMS, S.D. lab) for reading the manuscript. This work was supported by NIH grants S10RR027897 (TEM, UMMS), R01 GM051994-14 (S.D.), and R00 GM107355 (H.H.).
Publisher Copyright:
© 2016 Elsevier Ltd All rights reserved.
PY - 2016/3/21
Y1 - 2016/3/21
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cub.2016.01.025
DO - 10.1016/j.cub.2016.01.025
M3 - Article
C2 - 26948879
AN - SCOPUS:84959282659
SN - 0960-9822
VL - 26
SP - 793
EP - 801
JO - Current Biology
JF - Current Biology
IS - 6
ER -