Fig. 4 | Nature Communications

Fig. 4

From: The binding of Borealin to microtubules underlies a tension independent kinetochore-microtubule error correction pathway

Fig. 4

Mathematical model of tension-dependent and microtubule configuration-dependent phosphoregulation at kinetochores. a Upper box: schematic for kinase-phosphatase switch. Lower box: schematic for dynamically exchanging CPC pools. Kinase within each pool becomes activated by auto-phosphorylation and inactivated by soluble phosphatase, see Methods for details. Unless stated otherwise, calculations for all panels were done using model parameters listed in Supplementary Table 6 for different centromeric tension and/or microtubule configurations. b, c The concentration of chromatin-bound CPC kinase (gray, left axis) decreases from the middle of the centromere (centroid) to outer kinetochore containing Ndc80 substrate (shown with broken line). Because the total amount of chromatin-bound kinase does not change under tension, when chromatin is stretched, the kinase concentration is reduced throughout the centromere. Black lines (right axes) show the fraction of chromatin-bound kinase that is active; these curves drop abruptly due to bi-stability. Yellow dots show activity of chromatin-bound kinases at the Ndc80 location. These panels show tension-dependent model behavior in the absence of the microtubule-bound kinase pool \(\left( {k_{\mathrm {on}}^{\mathrm {MT}} = 0} \right)\). d, e Profiles as in c for different microtubule configurations: bi-oriented (green) or with centromere-proximal microtubules (red). Left axes—concentration of chromatin-bound kinase under tension (gray). Colored curves are plotted using the right axes, showing fraction of active kinase for all CPC pools (e) or only for the microtubule-bound pool (d). Colored dots show fraction of active kinase at Ndc80 site; the corresponding concentrations for dots on panel d are plotted in panel g “under tension”. f Spatial distribution of active microtubule-bound kinase (fraction from the microtubule-bound kinase pool) for different microtubule abundance (parameter α), see panel d for other details. Solid and dashed lines correspond to configurations with centromere-proximal and end-on microtubules, respectively. g Calculated concentration of active kinase (sum of all pools) at Ndc80 location of the kinetochore for indicated configurations. The last three columns correspond to model predictions in the presence of tension and centromere-proximal microtubules but either chromatin, microtubule or soluble CPC pools are eliminated. h Fractions of active kinase in all pools—microtubule-bound, chromatin-bound and soluble—respond to the size of centromere proximal microtubule bundle

Back to article page