Co-translational protein targeting facilitates centrosomal recruitment of PCNT during centrosome maturation in vertebrates

Elife. 2018 Apr 30:7:e34959. doi: 10.7554/eLife.34959.

Abstract

As microtubule-organizing centers of animal cells, centrosomes guide the formation of the bipolar spindle that segregates chromosomes during mitosis. At mitosis onset, centrosomes maximize microtubule-organizing activity by rapidly expanding the pericentriolar material (PCM). This process is in part driven by the large PCM protein pericentrin (PCNT), as its level increases at the PCM and helps recruit additional PCM components. However, the mechanism underlying the timely centrosomal enrichment of PCNT remains unclear. Here, we show that PCNT is delivered co-translationally to centrosomes during early mitosis by cytoplasmic dynein, as evidenced by centrosomal enrichment of PCNT mRNA, its translation near centrosomes, and requirement of intact polysomes for PCNT mRNA localization. Additionally, the microtubule minus-end regulator, ASPM, is also targeted co-translationally to mitotic spindle poles. Together, these findings suggest that co-translational targeting of cytoplasmic proteins to specific subcellular destinations may be a generalized protein targeting mechanism.

Keywords: cell biology; centrosome; human; mRNA localization; translation; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / genetics
  • Antigens / metabolism*
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Centrosome / metabolism*
  • Dyneins / metabolism*
  • Humans
  • Mitosis*
  • Nerve Tissue Proteins / metabolism
  • Protein Biosynthesis*
  • Protein Transport
  • RNA, Messenger / analysis
  • Zebrafish
  • Zebrafish Proteins / metabolism

Substances

  • ASPM protein, human
  • ASPM protein, zebrafish
  • Antigens
  • Cell Cycle Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Zebrafish Proteins
  • pericentrin
  • Dyneins