A communication hub for phosphoregulation of kinetochore-microtubule attachment

Proximity-based activation of AURORA A by MPS1 potentiates error correction

“…However, a pool of MPS1 still localizes to microtubule-attached kinetochores either through association with the NDC80 complex or other kinetochore receptors [7,12]. Three recent studies in budding yeast showed that MPS1 binds to regions in the CH-domains of the NDC80 complex that are on the opposite side of the microtubule binding region [16][17][18] and, accordingly, purified budding yeast NDC80 complex was shown to simultaneously bind microtubules and MPS1 in vitro [17]. It has been suggested that this interaction interface is conserved [18]; if so then this mechanism could explain how a population of MPS1 remains at microtubule-attached metazoan kinetochores.…”

“…Three recent studies in budding yeast showed that MPS1 binds to regions in the CH-domains of the NDC80 complex that are on the opposite side of the microtubule binding region [16][17][18] and, accordingly, purified budding yeast NDC80 complex was shown to simultaneously bind microtubules and MPS1 in vitro [17]. It has been suggested that this interaction interface is conserved [18]; if so then this mechanism could explain how a population of MPS1 remains at microtubule-attached metazoan kinetochores. Regardless of how it is recruited, we hypothesize that the residual MPS1 population on erroneously attached polar kinetochores activates AAK to promote their own correction.…”

“…The effect of MPS1 depletion on AAK activation was next examined following depolymerization of microtubules with colchicine since MPS1 becomes enriched at unattached kinetochores via direct interaction with the NDC80 complex [13][14][15][16][17][18]. High levels of AAK T311Ph were observed in control cells, but AAK activation was significantly compromised following depletion of either MPS1 or NDC80, which mis-localized MPS1 from kinetochores (Figures 1C, 1D and S1C).…”