beta-Catenin is a Nek2 substrate involved in centrosome separation.
beta-Catenin plays important roles in cell adhesion and gene transcription, and has been shown recently to be essential for the establishment of a bipolar mitotic spindle. Here we show that beta-catenin is a component of interphase centrosomes and that stabilization of beta-catenin, mimicking mutations found in cancers, induces centrosome splitting. Centrosomes are held together by a dynamic linker regulated by Nek2 kinase and its substrates C-Nap1 (centrosomal Nek2-associated protein 1) and Rootletin. We show that beta-catenin binds to and is phosphorylated by Nek2, and is in a complex with Rootletin. In interphase, beta-catenin colocalizes with Rootletin between C-Nap1 puncta at the proximal end of centrioles, and this localization is dependent on C-Nap1 and Rootletin. In mitosis, when Nek2 activity increases, beta-catenin localizes to centrosomes at spindle poles independent of Rootletin. Increased Nek2 activity disrupts the interaction of Rootletin with centrosomes and results in binding of beta-catenin to Rootletin-independent sites on centrosomes, an event that is required for centrosome separation. These results identify beta-catenin as a component of the intercentrosomal linker and define a new function for beta-catenin as a key regulator of mitotic centrosome separation.
Bahmanyar
Shirin
S
Department of Biological Sciences, Stanford University, Stanford, California 94305, USA.
Kaplan
Daniel D
DD
Deluca
Jennifer G
JG
Giddings
Thomas H
TH
O'Toole
Eileen T
ET
Winey
Mark
M
Salmon
Edward D
ED
Casey
Patrick J
PJ
Nelson
W James
WJ
Barth
Angela I M
AI
D000818:Animals; D051186:Armadillo Domain Proteins / Q000378:metabolism; D002478:Cells, Cultured; D018385:Centrosome / Q000201:enzymology / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D004285:Dogs; D006801:Humans; D007399:Interphase; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D051176:beta Catenin / Q000032:analysis / Q000378:metabolism*; D012359:tRNA Methyltransferases
D051186:Armadillo Domain Proteins; C499237:CROCC protein, human; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; D051176:beta Catenin; C498548:TRMO protein, human; D012359:tRNA Methyltransferases; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases