Seh1 targets GATOR2 and Nup153 to mitotic chromosomes

J Cell Sci. 2018 May 1;131(9):jcs213140. doi: 10.1242/jcs.213140.

Abstract

In metazoa, the Nup107 complex (also known as the nucleoporin Y-complex) plays a major role in formation of the nuclear pore complex in interphase and is localised to kinetochores in mitosis. The Nup107 complex shares a single highly conserved subunit, Seh1 (also known as SEH1L in mammals) with the GATOR2 complex, an essential activator of mTORC1 kinase. mTORC1/GATOR2 has a central role in the coordination of cell growth and proliferation. Here, we use chemical genetics and quantitative chromosome proteomics to study the role of the Seh1 protein in mitosis. Surprisingly, Seh1 is not required for the association of the Nup107 complex with mitotic chromosomes, but it is essential for the association of both the GATOR2 complex and nucleoporin Nup153 with mitotic chromosomes. Our analysis also reveals a role for Seh1 at human centromeres, where it is required for efficient localisation of the chromosomal passenger complex (CPC). Furthermore, this analysis detects a functional interaction between the Nup107 complex and the small kinetochore protein SKAP (also known as KNSTRN).

Keywords: CPC; Chromosome; GATOR2; Kinetochore microtubules; NPC; Nuclear pore complex; Nup153; Seh1; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Chromosomes, Human*
  • Gene Knockout Techniques
  • HCT116 Cells
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / genetics
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mitosis / genetics
  • Mitosis / physiology*
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism*
  • Transfection

Substances

  • Cell Cycle Proteins
  • NUP153 protein, human
  • Nuclear Pore Complex Proteins
  • Mechanistic Target of Rapamycin Complex 1