Kinesin-14 KIFC1 modulates spindle assembly and chromosome segregation in mouse spermatocytes

Exp Cell Res. 2022 May 1;414(1):113095. doi: 10.1016/j.yexcr.2022.113095. Epub 2022 Mar 5.

Abstract

Kinesin-14 KIFC1 regulates spindle assembly and centrosome clustering in diverse organisms during cell division. KIFC1 proteins are essential for spindle assembly and chromosome alignment in mitosis. However, the roles and mechanisms of KIFC1 proteins in male spermatocytes remain largely unknown. In this study, we reveal that KIFC1 proteins mainly accumulate at the centrosomes and central spindle in mouse spermatocytes both in vitro and in vivo. We utilize two KIFC1 specific inhibitors, AZ82 and CW069, for the inhibition of KIFC1 in mouse spermatogenic cells and cultured GC-2 spd(ts) cells. We find that KIFC1 inhibition results in the increase of spermatocytes with micronuclei, the disorganization of the meiotic spindles, and the formation of multiple centrosomes. Furthermore, we demonstrate that KIFC1 inhibition leads to spindle defects, chromosome misalignment and the formation of aneuploidy in cultured GC-2 spd(ts) cells. In this study, we reveal that KIFC1 proteins are critical for centrosome maintenance and chromosome stability in mouse spermatocytes.

Keywords: Centrosome; Chromosome; KIFC1; Meiosis; Microtubule; Spermatocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Centrosome / metabolism
  • Chromosome Segregation*
  • Kinesins* / genetics
  • Male
  • Meiosis
  • Mice
  • Mitosis
  • Spermatocytes
  • Spindle Apparatus / metabolism
  • beta Karyopherins / metabolism*

Substances

  • Kifc1 protein, mouse
  • beta Karyopherins
  • Kinesins