PRC1-labeled microtubule bundles and kinetochore pairs show one-to-one association in metaphase

EMBO Rep. 2017 Feb;18(2):217-230. doi: 10.15252/embr.201642650. Epub 2016 Dec 27.

Abstract

In the mitotic spindle, kinetochore microtubules form k-fibers, whereas overlap or interpolar microtubules form antiparallel arrays containing the cross-linker protein regulator of cytokinesis 1 (PRC1). We have recently shown that an overlap bundle, termed bridging fiber, links outermost sister k-fibers. However, the relationship between overlap bundles and k-fibers throughout the spindle remained unknown. Here, we show that in a metaphase spindle more than 90% of overlap bundles act as a bridge between sister k-fibers. We found that the number of PRC1-GFP-labeled bundles per spindle is nearly the same as the number of kinetochore pairs. Live-cell imaging revealed that kinetochore movement in the equatorial plane of the spindle is highly correlated with the movement of the coupled PRC1-GFP-labeled fiber, whereas the correlation with other fibers decreases with increasing distance. Analysis of endogenous PRC1 localization confirmed the results obtained with PRC1-GFP PRC1 knockdown reduced the bridging fiber thickness and interkinetochore distance throughout the spindle, suggesting a function of PRC1 in bridging microtubule organization and force balance in the metaphase spindle.

Keywords: bridging fiber; interpolar microtubules; k‐fiber; mitosis; overlap microtubules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosomes, Human
  • Gene Expression
  • Gene Silencing
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Metaphase*
  • Microtubules / metabolism*
  • Molecular Imaging / methods
  • Protein Transport
  • RNA, Small Interfering / genetics
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Spindle Apparatus*

Substances

  • Cell Cycle Proteins
  • PRC1 protein, human
  • RNA, Small Interfering
  • Recombinant Fusion Proteins