Spatial Positive Feedback at the Onset of Mitosis
نویسندگان
چکیده
Mitosis is triggered by the activation of Cdk1-cyclin B1 and its translocation from the cytoplasm to the nucleus. Positive feedback loops regulate the activation of Cdk1-cyclin B1 and help make the process irreversible and all-or-none in character. Here we examine whether an analogous process, spatial positive feedback, regulates Cdk1-cyclin B1 redistribution. We used chemical biology approaches and live-cell microscopy to show that nuclear Cdk1-cyclin B1 promotes the translocation of Cdk1-cyclin B1 to the nucleus. Mechanistic studies suggest that cyclin B1 phosphorylation promotes nuclear translocation and, conversely, nuclear translocation promotes cyclin B1 phosphorylation, accounting for the feedback. Interfering with the abruptness of Cdk1-cyclin B1 translocation affects the timing and synchronicity of subsequent mitotic events, underscoring the functional importance of this feedback. We propose that spatial positive feedback ensures a rapid, complete, robust, and irreversible transition from interphase to mitosis and suggest that bistable spatiotemporal switches may be widespread in biological regulation.
منابع مشابه
Robust Cell Size Checkpoint from Spatiotemporal Positive Feedback Loop in Fission Yeast
Cells must maintain appropriate cell size during proliferation. Size control may be regulated by a size checkpoint that couples cell size to cell division. Biological experimental data suggests that the cell size is coupled to the cell cycle in two ways: the rates of protein synthesis and the cell polarity protein kinase Pom1 provide spatial information that is used to regulate mitosis inhibito...
متن کاملPositive Feedback Keeps Duration of Mitosis Temporally Insulated from Upstream Cell-Cycle Events
Cell division is characterized by a sequence of events by which a cell gives rise to two daughter cells. Quantitative measurements of cell-cycle dynamics in single cells showed that despite variability in G1-, S-, and G2 phases, duration of mitosis is short and remarkably constant. Surprisingly, there is no correlation between cell-cycle length and mitotic duration, suggesting that mitosis is t...
متن کاملSpatial Control of Cytokinesis by Cdr2 Kinase and Mid1/Anillin Nuclear Export
Maintaining genome integrity and cellular function requires proper positioning of the cell division plane. In most eukaryotes, cytokinesis relies on a contractile actomyosin ring positioned by intrinsic spatial signals that are poorly defined at the molecular level. Fission yeast cells assemble a medial contractile ring in response to positive spatial cues from the nucleus at the cell center an...
متن کاملFeedback control of the metaphase-anaphase transition in sea urchin zygotes: role of maloriented chromosomes
To help ensure the fidelity of chromosome transmission during mitosis, sea urchin zygotes have feedback control mechanisms for the metaphase-anaphase transition that monitor the assembly of spindle microtubules and the complete absence of proper chromosome attachment to the spindle. The way in which these feedback controls work has not been known. In this study we directly test the proposal tha...
متن کاملErratum: Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit
Correct execution of mitosis in eukaryotes relies on timely activation and inactivation of cyclin B-dependent kinase 1 (cdk1), the M-phase-promoting factor (MPF). Once activated, MPF is sustained until mitotic spindle assembly by phosphorylation-dependent feedback loops that prevent inhibitory phosphorylation of cdk1 and ubiquitin-dependent degradation of cyclin B. Whether subsequent MPF inacti...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cell
دوره 149 شماره
صفحات -
تاریخ انتشار 2012