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

Mei Zhu, Florian Settele, Sachin Kotak, Luis Sanchez-Pulido, Lena Ehret, Chris P Ponting, Pierre Gönczy, Ingrid Hoffmann

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)773-87
Number of pages15
JournalJournal of Cell Biology
Volume200
Issue number6
DOIs
Publication statusPublished - 18 Mar 2013

Keywords

  • Anaphase
  • Cell Cycle Proteins
  • Dyneins
  • HeLa Cells
  • Humans
  • Metaphase
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Microtubules
  • Phosphoproteins
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Spindle Apparatus

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