TY - JOUR
T1 - Chromosome misalignment is associated with PLK1 activity at cenexin-positive mitotic centrosomes
AU - Colicino, Erica G.
AU - Stevens, Katrina
AU - Curtis, Erin
AU - Rathbun, Lindsay
AU - Bates, Michael
AU - Manikas, Julie
AU - Amack, Jeffrey
AU - Freshour, Judy
AU - Hehnly, Heidi
N1 - Funding Information:
This work was supported by National Institutes of Health Grants no. R00GM107355 and no. R01GM127621 (to H.H.) and the Carol Baldwin Foundation of Central New York (to H.H. while at SUNY Upstate Medical University). This work was supported by the U.S. Army Medical Research Acquisition Activity through the FY 16 Prostate Cancer Research Programs under Award no. W81XWH-17-1-0241 (to H.H.). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. We thank Patrick Meraldi for providing us the centrin-GFP/CENPA-mCherry HeLa cell line (Gasic et al., 2015) and Patrina Pellet (previously at G.E.) for assistance obtaining SIM images. We thank Dan Bergstralh (University of Rochester), Wenyi Feng, Leszek Kotula, and David Pruyne (SUNY Upstate Medical University) for careful edits and suggestions on earlier versions of this article.
Publisher Copyright:
© 2019 Colicino et al.
PY - 2019/6/15
Y1 - 2019/6/15
N2 - The mitotic kinase, polo-like kinase 1 (PLK1), facilitates the assembly of the two mitotic spindle poles, which are required for the formation of the microtubule-based spindle that ensures appropriate chromosome distribution into the two forming daughter cells. Spindle poles are asymmetric in composition. One spindle pole contains the oldest mitotic centriole, the mother centriole, where the majority of cenexin, the mother centriole appendage protein and PLK1 binding partner, resides. We hypothesized that PLK1 activity is greater at the cenexin-positive older spindle pole. Our studies found that PLK1 asymmetrically localizes between spindle poles under conditions of chromosome misalignment, and chromosomes tend to misalign toward the oldest spindle pole in a cenexin- and PLK1-dependent manner. During chromosome misalignment, PLK1 activity is increased specifically at the oldest spindle pole, and this increase in activity is lost in cenexin-depleted cells. We propose a model where PLK1 activity elevates in response to misaligned chromosomes at the oldest spindle pole during metaphase.
AB - The mitotic kinase, polo-like kinase 1 (PLK1), facilitates the assembly of the two mitotic spindle poles, which are required for the formation of the microtubule-based spindle that ensures appropriate chromosome distribution into the two forming daughter cells. Spindle poles are asymmetric in composition. One spindle pole contains the oldest mitotic centriole, the mother centriole, where the majority of cenexin, the mother centriole appendage protein and PLK1 binding partner, resides. We hypothesized that PLK1 activity is greater at the cenexin-positive older spindle pole. Our studies found that PLK1 asymmetrically localizes between spindle poles under conditions of chromosome misalignment, and chromosomes tend to misalign toward the oldest spindle pole in a cenexin- and PLK1-dependent manner. During chromosome misalignment, PLK1 activity is increased specifically at the oldest spindle pole, and this increase in activity is lost in cenexin-depleted cells. We propose a model where PLK1 activity elevates in response to misaligned chromosomes at the oldest spindle pole during metaphase.
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U2 - 10.1091/mbc.E18-12-0817
DO - 10.1091/mbc.E18-12-0817
M3 - Article
C2 - 31042116
AN - SCOPUS:85068198024
SN - 1059-1524
VL - 30
SP - 1598
EP - 1609
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 13
ER -