β-catenin at the centrosome: discrete pools of β-catenin communicate during mitosis and may co-ordinate centrosome functions and cell cycle progression

Abstract

Beta-catenin is a multifunctional protein with critical roles in cell-cell adhesion, Wnt-signaling and the centrosome cycle. Whereas the roles of β-catenin in cell-cell adhesion and Wnt-signaling have been studied extensively, the mechanism(s) involving β-catenin in centrosome functions are poorly understood. β-Catenin localizes to centrosomes and promotes mitotic progression. NIMA-related protein kinase 2 (Nek2), which stimulates centrosome separation, binds to and phosphorylates β-catenin. β-Catenin interacting proteins involved in Wnt signaling such as adenomatous polyposis coli, Axin, and GSK3β, are also localized at centrosomes and play roles in promoting mitotic progression. Additionally, proteins associated with cell-cell adhesion sites, such as dynein, regulate mitotic spindle positioning. These roles of proteins at the cell cortex and Wnt signaling that involve β-catenin indicate a cross-talk between different sub-cellular sites in the cell at mitosis, and that different pools of β-catenin may co-ordinate centrosome functions and cell cycle progression.

Keywords: centrosomes; mitotic spindle; β-catenin.

Figure 1

β-Catenin is a multifunctional protein that localizes at cell-cell contacts, the nucleus, cytosol and centrosomes. Cortical proteins and Wnt signaling components have been implicated in regulating cell cycle progression. Additionally, β-catenin destruction pathway proteins (APC, Axin, GSK3β) are also located at the centrosome and are involved in similar functions as β-catenin suggesting a cross-talk between these 3 distinct cellular pools of proteins.

Figure 2

PLK1 is upstream of Nek2 in promoting removal of the centriolar linker at the G2/M transition. PLK1 also negative regulates the dynein-dynactin complex at the cell cortex in order to ensure proper spindle positioning. These processes promote mitotic spindle formation and centrosome separation during cell division.