Kinesin 5B (KIF5B) Is Required for Progression through Female Meiosis and Proper Chromosomal Segregation in Mitotic Cells

Dawit Kidane,Denny Sakkas,James Mcgrath,Joann B Sweasy,Timothy Nottoli,Barbara G Mellone

doi:10.1371/journal.pone.0058585

Dawit Kidane, Denny Sakkas + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0058585

Copy DOI

Journal: PloS one	Publication Date: Apr 1, 2013
Citations: 47	License type: CC BY 4.0

Affiliation: Yale Cancer Center, Yale University

Abstract

The fidelity of chromosomal segregation during cell division is important to maintain chromosomal stability in order to prevent cancer and birth defects. Although several spindle-associated molecular motors have been shown to be essential for cell division, only a few chromosome arm-associated motors have been described. Here, we investigated the role of Kinesin 5b (Kif5b) during female mouse meiotic cell development and mitotic cell division. RNA interference (RNAi)-mediated silencing of Kif5b in mouse oocytes induced significant delay in germinal vesicle breakdown (GVBD) and failure in extrusion of the first polar body (PBE). In mitotic cells, knockdown of Kif5b leads to centrosome amplification and a chromosomal segregation defect. These data suggest that KIF5B is critical in suppressing chromosomal instability at the early stages of female meiotic cell development and mitotic cell division.

Highlights

Spatial and temporal control of cell division is essential to ensure the equal segregation of genetic material between daughter cells
KIF5B is critical for germinal vesicle breakdown (GVBD) and polar body exclusion
To determine if KIF5B is critical for meiotic progression, meiotically competent germinal vesicle intact oocytes were microinjected with RNA interference (RNAi) against Kif5b and monitored for 16 hr

Summary

Introduction

Spatial and temporal control of cell division is essential to ensure the equal segregation of genetic material between daughter cells. Chromosome segregation in mitosis and meiosis is directed by kinetochores, which regulate the attachment and movement of chromosomes on the spindle and ensure the fidelity of segregation [1,2]. Disjunction of maternal from paternal centromeres depends on the attachment of sister kinetochores to microtubules emanating from the same pole. Remodeling of chromosomes during oocyte meiosis begins when homologues initially pair and condense via actions of the synaptonemal complex proteins (SC) during initiation of prophase I, followed by homologous recombination and crossing-over events [3]. A bipolar meiotic spindle forms, consisting of polymerized microtubules, and attaches to homologues at their centromeres. Physical contact between homologous pairs at chiasmata counteracts forces pulling apart homologues, resulting in alignment of chromosomes along the metaphase plate, signaling completion of metaphase I (MI). Forces moving toward and away from the pole balance each other during metaphase congression and are responsible for chromosome motility toward the poles [5]

Methods

Results

Conclusion