Nucleoporin Nup62 maintains centrosome homeostasis

Cell Cycle. 2013 Dec 15;12(24):3804-16. doi: 10.4161/cc.26671. Epub 2013 Oct 7.

Abstract

Centrosomes are comprised of 2 orthogonally arranged centrioles surrounded by the pericentriolar material (PCM), which serves as the main microtubule organizing center of the animal cell. More importantly, centrosomes also control spindle polarity and orientation during mitosis. Recently, we and other investigators discovered that several nucleoporins play critical roles during cell division. Here, we show that nucleoporin Nup62 plays a novel role in centrosome integrity. Knockdown of Nup62 induced mitotic arrest in G 2/M phases and mitotic cell death. Depletion of Nup62 using RNA interference results in defective centrosome segregation and centriole maturation during the G 2 phase. Moreover, Nup62 depletion in human cells leads to the appearance of multinucleated cells and induces the formation of multipolar centrosomes, centriole synthesis defects, dramatic spindle orientation defects, and centrosome component rearrangements that impair cell bi-polarity. Our results also point to a potential role of Nup62 in targeting gamma-tubulin and SAS-6 to the centrioles.

Keywords: Nup62; SAS-6; centriole; centrosome; gamma-tubulin; nucleoporin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Centrioles / physiology
  • Centrosome / physiology*
  • G2 Phase Cell Cycle Checkpoints
  • Homeostasis
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Mice
  • Mitosis
  • Nuclear Pore Complex Proteins / metabolism*
  • Spindle Apparatus / physiology
  • Tubulin / metabolism

Substances

  • NUP62 protein, mouse
  • Nuclear Pore Complex Proteins
  • Tubulin