MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression

J Cell Biol. 2013 Mar 18;200(6):773-87. doi: 10.1083/jcb.201207050.

Abstract

Precise positioning of the mitotic spindle determines the correct cell division axis and is crucial for organism development. Spindle positioning is mediated through a cortical machinery by capturing astral microtubules, thereby generating pushing/pulling forces at the cell cortex. However, the molecular link between these two structures remains elusive. Here we describe a previously uncharacterized protein, MISP (C19orf21), as a substrate of Plk1 that is required for correct mitotic spindle positioning. MISP is an actin-associated protein throughout the cell cycle. MISP depletion led to an impaired metaphase-to-anaphase transition, which depended on phosphorylation by Plk1. Loss of MISP induced mitotic defects including spindle misorientation accompanied by shortened astral microtubules. Furthermore, we find that MISP formed a complex with and regulated the cortical distribution of the +TIP binding protein p150(glued), a subunit of the dynein-dynactin complex. We propose that Plk1 phosphorylates MISP, thus stabilizing cortical and astral microtubule attachments required for proper mitotic spindle positioning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Dynactin Complex
  • Dyneins / genetics
  • Dyneins / metabolism
  • HeLa Cells
  • Humans
  • Metaphase / physiology*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / genetics
  • Microtubules / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation / physiology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*

Substances

  • Cell Cycle Proteins
  • DCTN1 protein, human
  • Dynactin Complex
  • MISP protein, human
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • Dyneins