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

Article Details

Citation

Zhu M, Settele F, Kotak S, Sanchez-Pulido L, Ehret L, Ponting CP, Gonczy P, Hoffmann I

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.

PubMed ID
23509069 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Focal adhesion kinase 1Q05397Details
Serine/threonine-protein kinase PLK1P53350Details