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A cell separation checkpoint that enforces the proper order of late cytokinetic events.

ABSTRACT: Eukaryotic cell division requires dependency relationships in which late processes commence only after early ones are appropriately completed. We have discovered a system that blocks late events of cytokinesis until early ones are successfully accomplished. In budding yeast, cytokinetic actomyosin ring contraction and membrane ingression are coupled with deposition of an extracellular septum that is selectively degraded in its primary septum immediately after its completion by secreted enzymes. We find this secretion event is linked to septum completion and forestalled when the process is slowed. Delay of septum degradation requires Fir1, an intrinsically disordered protein localized to the cytokinesis site that is degraded upon septum completion but stabilized when septation is aberrant. Fir1 protects cytokinesis in part by inhibiting a separation-specific exocytosis function of the NDR/LATS kinase Cbk1, a key component of "hippo" signaling that induces mother-daughter separation. We term this system enforcement of cytokinesis order, a checkpoint ensuring proper temporal sequence of mechanistically incompatible processes of cytokinesis.

SUBMITTER: Brace JL

PROVIDER: S-EPMC6314563 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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A cell separation checkpoint that enforces the proper order of late cytokinetic events.

Brace Jennifer L JL Doerfler Matthew D MD Weiss Eric L EL

The Journal of cell biology 20181119 1

Eukaryotic cell division requires dependency relationships in which late processes commence only after early ones are appropriately completed. We have discovered a system that blocks late events of cytokinesis until early ones are successfully accomplished. In budding yeast, cytokinetic actomyosin ring contraction and membrane ingression are coupled with deposition of an extracellular septum that is selectively degraded in its primary septum immediately after its completion by secreted enzymes. ...[more]

PMID: 30455324

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Project description:BACKGROUND: Temporal sequence represents the main principle underlying episodic memory. The storage of temporal sequence information is thought to involve hippocampus-dependent memory systems, preserving temporal structure possibly via chaining of sequence elements in heteroassociative networks. Converging evidence indicates that sleep enhances the consolidation of recently acquired representations in the hippocampus-dependent declarative memory system. Yet, it is unknown if this consolidation process comprises strengthening of the temporal sequence structure of the representation as well, or is restricted to sequence elements independent of their temporal order. To address this issue we tested the influence of sleep on the strength of forward and backward associations in word-triplets. METHODOLOGY/PRINCIPAL FINDINGS: Subjects learned a list of 32 triplets of unrelated words, presented successively (A-B-C) in the center of a screen, and either slept normally or stayed awake in the subsequent night. After two days, retrieval was assessed for the triplets sequentially either in a forward direction (cueing with A and B and asking for B and C, respectively) or in a backward direction (cueing with C and B and asking for B and A, respectively). Memory was better for forward than backward associations (p<0.01). Sleep did not affect backward associations, but enhanced forward associations, specifically for the first (AB) transitions (p<0.01), which were generally more difficult to retrieve than the second transitions. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that consolidation during sleep strengthens the original temporal sequence structure in memory, presumably as a result of a replay of new representations during sleep in forward direction. Our finding suggests that the temporally directed replay of memory during sleep, apart from strengthening those traces, could be the key mechanism that explains how temporal order is integrated and maintained in the trace of an episodic memory.

Project description:BackgroundDiverse mitotic events can be triggered in the correct order and time by a single cyclin-CDK. A single regulator could confer order and timing on multiple events if later events require higher cyclin-CDK than earlier events, so that gradually rising cyclin-CDK levels can sequentially trigger responsive events: the "quantitative model" of ordering.Methodology/principal findingsThis 'quantitative model' makes predictions for the effect of locking cyclin at fixed levels for a protracted period: at low cyclin levels, early events should occur rapidly, while late events should be slow, defective, or highly variable (depending on threshold mechanism). We titrated the budding yeast mitotic cyclin Clb2 within its endogenous expression range to a stable, fixed level and measured time to occurrence of three mitotic events: growth depolarization, spindle formation, and spindle elongation, as a function of fixed Clb2 level. These events require increasingly more Clb2 according to their normal order of occurrence. Events occur efficiently and with low variability at fixed Clb2 levels similar to those observed when the events normally occur. A second prediction of the model is that increasing the rate of cyclin accumulation should globally advance timing of all events. Moderate (<2-fold) overexpression of Clb2 accelerates all events of mitosis, resulting in consistently rapid sequential cell cycles. However, this moderate overexpression also causes a significant frequency of premature mitoses leading to inviability, suggesting that Clb2 expression level is optimized to balance the fitness costs of variability and catastrophe.Conclusions/significanceWe conclude that mitotic events are regulated by discrete cyclin-CDK thresholds. These thresholds are sequentially triggered as cyclin increases, yielding reliable order and timing. In many biological processes a graded input must be translated into discrete outputs. In such systems, expression of the central regulator is likely to be tuned to an optimum level, as we observe here for Clb2.

Dataset Information

A cell separation checkpoint that enforces the proper order of late cytokinetic events.

Publications

A cell separation checkpoint that enforces the proper order of late cytokinetic events.

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