title: MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression.
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.
authors.affiliation: Cell Cycle Control and Carcinogenesis, German Cancer Research Center, DKFZ, D-69120 Heidelberg, Germany.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhu
authors.forename: Florian
authors.initials: F
authors.lastname: Settele
authors.forename: Sachin
authors.initials: S
authors.lastname: Kotak
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez-Pulido
authors.forename: Lena
authors.initials: L
authors.lastname: Ehret
authors.forename: Chris P
authors.initials: CP
authors.lastname: Ponting
authors.forename: Pierre
authors.initials: P
authors.lastname: Gönczy
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hoffmann
mesh_terms: D000705:Anaphase / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D000072159:Dynactin Complex; D004398:Dyneins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase / Q000502:physiology*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D000072159:Dynactin Complex; D004398:Dyneins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C000606360:DCTN1 protein, human; C581267:MISP protein, human