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

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 mole...

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Main Authors: Zhu, M, Settele, F, Kotak, S, Sanchez-Pulido, L, Ehret, L, Ponting, C, Gönczy, P, Hoffmann, I
Format: Journal article
Language:English
Published: 2013
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author Zhu, M
Settele, F
Kotak, S
Sanchez-Pulido, L
Ehret, L
Ponting, C
Gönczy, P
Hoffmann, I
author_facet Zhu, M
Settele, F
Kotak, S
Sanchez-Pulido, L
Ehret, L
Ponting, C
Gönczy, P
Hoffmann, I
author_sort Zhu, M
collection OXFORD
description 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.
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spelling oxford-uuid:b28026ad-80b0-4aed-bb5c-0c99835053ae2022-03-27T04:12:10ZMISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b28026ad-80b0-4aed-bb5c-0c99835053aeEnglishSymplectic Elements at Oxford2013Zhu, MSettele, FKotak, SSanchez-Pulido, LEhret, LPonting, CGönczy, PHoffmann, IPrecise 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.
spellingShingle Zhu, M
Settele, F
Kotak, S
Sanchez-Pulido, L
Ehret, L
Ponting, C
Gönczy, P
Hoffmann, I
MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression.
title MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression.
title_full MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression.
title_fullStr MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression.
title_full_unstemmed MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression.
title_short MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression.
title_sort misp is a novel plk1 substrate required for proper spindle orientation and mitotic progression
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