14-3-3 regulation of Ncd reveals a new mechanism for targeting proteins to the spindle in oocytes

J Cell Biol. 2017 Oct 2;216(10):3029-3039. doi: 10.1083/jcb.201704120. Epub 2017 Aug 31.

Abstract

The meiotic spindle is formed without centrosomes in a large volume of oocytes. Local activation of crucial spindle proteins around chromosomes is important for formation and maintenance of a bipolar spindle in oocytes. We found that phosphodocking 14-3-3 proteins stabilize spindle bipolarity in Drosophila melanogaster oocytes. A critical 14-3-3 target is the minus end-directed motor Ncd (human HSET; kinesin-14), which has well-documented roles in stabilizing a bipolar spindle in oocytes. Phospho docking by 14-3-3 inhibits the microtubule binding activity of the nonmotor Ncd tail. Further phosphorylation by Aurora B kinase can release Ncd from this inhibitory effect of 14-3-3. As Aurora B localizes to chromosomes and spindles, 14-3-3 facilitates specific association of Ncd with spindle microtubules by preventing Ncd from binding to nonspindle microtubules in oocytes. Therefore, 14-3-3 translates a spatial cue provided by Aurora B to target Ncd selectively to the spindle within the large volume of oocytes.

MeSH terms

  • 14-3-3 Proteins / genetics
  • 14-3-3 Proteins / metabolism*
  • Animals
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism
  • Chromosomes, Insect / genetics
  • Chromosomes, Insect / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Female
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Microtubules / genetics
  • Microtubules / metabolism*
  • Oocytes / cytology
  • Oocytes / metabolism*
  • Protein Transport / physiology
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*

Substances

  • 14-3-3 Proteins
  • Drosophila Proteins
  • ncd protein, Drosophila
  • AurB protein, Drosophila
  • Aurora Kinase B
  • Kinesins