PUBLICATION

Chromosome misalignment is associated with PLK1 activity at cenexin-positive mitotic centrosomes

Authors
Colicino, E.G., Stevens, K., Curtis, E., Rathbun, L., Bates, M., Manikas, J., Amack, J., Freshour, J., Hehnly, H.
ID
ZDB-PUB-190507-4
Date
2019
Source
Molecular biology of the cell   30(13): 1598-1609 (Journal)
Registered Authors
Amack, Jeffrey, Hehnly, Heidi
Keywords
none
MeSH Terms
  • Animals
  • Cell Cycle Proteins/genetics
  • Cell Cycle Proteins/metabolism*
  • Centrioles/metabolism
  • Centrosome/metabolism
  • Chromosome Segregation/physiology*
  • Chromosomes/metabolism
  • HeLa Cells
  • Heat-Shock Proteins/metabolism
  • Heat-Shock Proteins/physiology
  • Humans
  • Microtubules/metabolism
  • Mitosis/physiology
  • Protein Serine-Threonine Kinases/genetics
  • Protein Serine-Threonine Kinases/metabolism*
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins/metabolism*
  • Spindle Apparatus/metabolism
  • Spindle Poles/enzymology
  • Spindle Poles/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
31042116 Full text @ Mol. Biol. Cell
Abstract
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 towards 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. Video S1 Video S1 PLK1-mCherry is enriched at spindle poles, kinetochores, and cytokinetic midbody in live zebrafish embryos. Maximum confocal micrographs of a single mitotic cell in a live zebrafish embryo (4.5 hpf) expressing PLK1-mCherry from prometaphase through cytokinesis. Images from every 60 seconds, over 6 minutes. Bar = 10μm. Video S2 Video S2 PLK1-GFP asymmetrically distributes and is exchanged at the two spindle poles during metaphase. Fluorescence recovery after photobleaching of RPE cells stably expressing GFP-PLK1 at mitotic centrosomes during metaphase. Images taken every 113 milliseconds for 18 seconds. (Fire-LUT, ImageJ). Bar = 5μm. Video S3 Video S3 Chromosomes predominately misalign toward the oldest spindle pole in a cenexin-dependent manner. Maximum confocal micrographs of single HeLa cells stably expressing CENPA-mCherry (black) and either control (left) or cenexin (right) shRNA from prometaphase/metaphase through cytokinesis. Images taken every 3 seconds for 84 seconds. Bar = 5μm.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping