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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 150-170 |
| Number of pages | 21 |
| Journal | Journal of Cell Biology |
| Volume | 218 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2019 |
Funding
We thank members of the Weiss and L. Lackner laboratories at Northwestern University for critical review of the manuscript. We thank K. Labib, G. Pereria (German Cancer Research Center, Heidelberg, Germany), F. Cross, E. Bi, R. Lamb, Y. Barral, and S. Strahl for strains, plasmids, and antibodies. We thank C. Wilke (Northwestern University, Biological Imaging Facility) for assistance with electron microscopy and E. Anderson and S. Zdraljevic (Northwestern University) for assistance with R software (statistical analysis and graphing). We also thank staff and instrumentation assistance from Northwestern University\u2019s Biological Imaging Facility, which is supported by the Chemistry for Life Processes Institute and the Northwestern Office for Research, and from the Northwestern University\u2019s High Throughput Analysis Laboratory, which is a core facility of the Lurie Cancer Center (grant #P30CA060553) . Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R01GM084223 to E.L. Weiss. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing financial interests.
ASJC Scopus subject areas
- Cell Biology