Kinetochore Recruitment of the Spindle and Kinetochore-Associated (Ska) Complex Is Regulated by Centrosomal PP2A in Caenorhabditis elegans

Genetics. 2019 Jun;212(2):509-522. doi: 10.1534/genetics.119.302105. Epub 2019 Apr 24.

Abstract

During mitosis, kinetochore-microtubule interactions ensure that chromosomes are accurately segregated to daughter cells. RSA-1 (regulator of spindle assembly-1) is a regulatory B″ subunit of protein phosphatase 2A that was previously proposed to modulate microtubule dynamics during spindle assembly. We have identified a genetic interaction between the centrosomal protein, RSA-1, and the spindle- and kinetochore-associated (Ska) complex in Caenorhabditis elegans In a forward genetic screen for suppressors of rsa-1(or598) embryonic lethality, we identified mutations in ska-1 and ska-3 Loss of SKA-1 and SKA-3, as well as components of the KMN (KNL-1/MIS-12/NDC-80) complex and the microtubule end-binding protein EBP-2, all suppressed the embryonic lethality of rsa-1(or598) These suppressors also disrupted the intracellular localization of the Ska complex, revealing a network of proteins that influence Ska function during mitosis. In rsa-1(or598) embryos, SKA-1 is excessively and prematurely recruited to kinetochores during spindle assembly, but SKA-1 levels return to normal just prior to anaphase onset. Loss of the TPX2 homolog, TPXL-1, also resulted in overrecruitment of SKA-1 to the kinetochores and this correlated with the loss of Aurora A kinase on the spindle microtubules. We propose that rsa-1 regulates the kinetochore localization of the Ska complex, with spindle-associated Aurora A acting as a potential mediator. These data reveal a novel mechanism of protein phosphatase 2A function during mitosis involving a centrosome-based regulatory mechanism for Ska complex recruitment to the kinetochore.

Keywords: Aurora kinase; C. elegans; PP2A phosphatase; Ska complex; TPX2; centrosome; kinetochore; microtubule; spindle assembly.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase / genetics
  • Animals
  • Aurora Kinase A / metabolism
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Carrier Proteins / metabolism
  • Centrosome / metabolism
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation / genetics
  • Kinesins / metabolism
  • Kinetochores / metabolism*
  • Microtubule Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism*
  • Mitosis / genetics
  • Protein Phosphatase 2 / genetics*
  • Protein Phosphatase 2 / metabolism
  • Spindle Apparatus / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Chromosomal Proteins, Non-Histone
  • KNL-1 protein, C elegans
  • Microtubule Proteins
  • Microtubule-Associated Proteins
  • NDC-80 protein, C elegans
  • TPXL-1 protein, C elegans
  • ska-1 protein, C elegans
  • Aurora Kinase A
  • Protein Phosphatase 2
  • rsa-1 protein, C elegans
  • klp-7 protein, C elegans
  • Kinesins

Associated data

  • figshare/10.25386/genetics.8031848