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Mitotic catenation is monitored and resolved by a PKC?-regulated pathway.

ABSTRACT: Exit from mitosis is controlled by silencing of the spindle assembly checkpoint (SAC). It is important that preceding exit, all sister chromatid pairs are correctly bioriented, and that residual catenation is resolved, permitting complete sister chromatid separation in the ensuing anaphase. Here we determine that the metaphase response to catenation in mammalian cells operates through PKC?. The PKC?-controlled pathway regulates exit from the SAC only when mitotic cells are challenged by retained catenation and this delayed exit is characterized by BubR1-high and Mad2-low kinetochores. In addition, we show that this pathway is necessary to facilitate resolution of retained catenanes in mitosis. When delayed by catenation in mitosis, inhibition of PKC? results in premature entry into anaphase with PICH-positive strands and chromosome bridging. These findings demonstrate the importance of PKC?-mediated regulation in protection from loss of chromosome integrity in cells failing to resolve catenation in G2.

SUBMITTER: Brownlow N

PROVIDER: S-EPMC4272242 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Mitotic catenation is monitored and resolved by a PKCε-regulated pathway.

Brownlow Nicola N Pike Tanya T Zicha Daniel D Collinson Lucy L Parker Peter J PJ

Nature communications 20141208

Exit from mitosis is controlled by silencing of the spindle assembly checkpoint (SAC). It is important that preceding exit, all sister chromatid pairs are correctly bioriented, and that residual catenation is resolved, permitting complete sister chromatid separation in the ensuing anaphase. Here we determine that the metaphase response to catenation in mammalian cells operates through PKCε. The PKCε-controlled pathway regulates exit from the SAC only when mitotic cells are challenged by retained ...[more]

PMID: 25483024

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Project description:Regulation of myosin light chain phosphatase (MLCP) via protein kinase C (PKC) and the 17 kDa PKC-potentiated inhibitor of myosin light chain phosphatase (CPI-17) has been reported as a Ca(2+) sensitization signaling pathway in smooth muscle (SM), and thus may be involved in tonic vs. phasic contractions. This study examined the protein expression and spatial-temporal distribution of PKC? and CPI-17 in intact SM tissues. KCl or carbachol (CCh) stimulation of tonic stomach fundus SM generates a sustained contraction while the phasic stomach antrum generates a transient contraction. In addition, the tonic fundus generates greater relative force than phasic antrum with 1 µM phorbol 12, 13-dibutyrate (PDBu) stimulation which is reported to activate the PKC? - CPI-17 pathway. Western blot analyses demonstrated that this contractile difference was not caused by a difference in the protein expression of PKC? or CPI-17 between these two tissues. Immunohistochemical results show that the distribution of PKC? in the longitudinal and circular layers of the fundus and antrum do not differ, being predominantly localized near the SM cell plasma membrane. Stimulation of either tissue with 1 µM PDBu or 1 µM CCh does not alter this peripheral PKC? distribution. There are no differences between these two tissues for the CPI-17 distribution, but unlike the PKC? distribution, CPI-17 appears to be diffusely distributed throughout the cytoplasm under relaxed tissue conditions but shifts to a primarily peripheral distribution at the plasma membrane with stimulation of the tissues with 1 µM PDBu or 1 µM CCh. Results from double labeling show that neither PKC? nor CPI-17 co-localize at the adherens junction (vinculin/talin) at the membrane but they do co-localize with each other and with caveoli (caveolin) at the membrane. This lack of difference suggests that the PKC? - CPI-17 pathway is not responsible for the tonic vs. phasic contractions observed in stomach fundus and antrum.

Dataset Information

Mitotic catenation is monitored and resolved by a PKC?-regulated pathway.

Publications

Mitotic catenation is monitored and resolved by a PKCε-regulated pathway.

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