title: Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction.
abstract: During interphase, centrosomes are held together by a proteinaceous linker that connects the proximal ends of the mother and daughter centriole. This linker is disassembled at the onset of mitosis in a process known as centrosome disjunction, thereby facilitating centrosome separation and bipolar spindle formation. The NIMA (never in mitosis A)-related kinase Nek2A is implicated in disconnecting the centrosomes through disjoining the linker proteins C-Nap1 and rootletin. However, the mechanisms controlling centrosome disjunction remain poorly understood. Here, we report that two Hippo pathway components, the mammalian sterile 20-like kinase 2 (Mst2) and the scaffold protein Salvador (hSav1), directly interact with Nek2A and regulate its ability to localize to centrosomes, and phosphorylate C-Nap1 and rootletin. Furthermore, we demonstrate that the hSav1-Mst2-Nek2A centrosome disjunction pathway becomes essential for bipolar spindle formation on partial inhibition of the kinesin-5 Eg5. We propose that hSav1-Mst2-Nek2A and Eg5 have distinct, but complementary functions, in centrosome disjunction.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, 69117 Heidelberg, Germany.
authors.forename: Balca R
authors.initials: BR
authors.lastname: Mardin
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lange
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Baxter
authors.forename: Tara
authors.initials: T
authors.lastname: Hardy
authors.forename: Sebastian R
authors.initials: SR
authors.lastname: Scholz
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Fry
authors.forename: Elmar
authors.initials: E
authors.lastname: Schiebel
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D006801:Humans; D007399:Interphase; D008969:Molecular Sequence Data; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016415:Sequence Alignment; D000090742:Serine-Threonine Kinase 3; D000099317:Hippo Kinases
chemical_list: D018797:Cell Cycle Proteins; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; C415864:SAV1 protein, human; C089441:NEK2 protein, human; C097835:STK3 protein, human; D000099317:Hippo Kinases