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

• Published in: The Journal of cell biology Vol. 218; no. 1; pp. 150 - 170
• Main Authors: Brace, Jennifer L, Doerfler, Matthew D, Weiss, Eric L
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 07.01.2019
• Subjects: Actomyosin; Actomyosin - genetics; Actomyosin - metabolism; Biodegradation; Cell division; Cell Division - drug effects; Cell Division - genetics; Cells; Contraction; Cytokines; Cytokinesis; Cytokinesis - drug effects; Cytokinesis - genetics; Degradation; Dependence; Enzymes; Exocytosis; Exocytosis - drug effects; Gene Expression Regulation, Fungal; Indoleacetic Acids - pharmacology; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Membranes; mRNA Cleavage and Polyadenylation Factors - genetics; mRNA Cleavage and Polyadenylation Factors - metabolism; Protein Stability - drug effects; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Proteolysis; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Separation; Septation; Septum; Signal Transduction; Yeast
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201805100

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.