Abstract
Cytokinesis requires the spatio-temporal coordination of membrane deposition and primary septum (PS) formation at the division site to drive acto-myosin ring (AMR) constriction. It has been demonstrated that AMR constriction invariably occurs only after the mitotic spindle disassembly. It has also been established that Chitin Synthase II (Chs2p) neck localization precedes mitotic spindle disassembly during mitotic exit. As AMR constriction depends upon PS formation, the question arises as to how chitin deposition is regulated so as to prevent premature AMR constriction and mitotic spindle breakage. In this study, we propose that cells regulate the coordination between spindle disassembly and AMR constriction via timely endocytosis of cytokinetic enzymes, Chs2p, Chs3p, and Fks1p. Inhibition of endocytosis leads to over accumulation of cytokinetic enzymes during mitotic exit, which accelerates the constriction of the AMR, and causes spindle breakage that eventually could contribute to monopolar spindle formation in the subsequent round of cell division. Intriguingly, the mitotic spindle breakage observed in endocytosis mutants can be rescued either by deleting or inhibiting the activities of, CHS2, CHS3 and FKS1, which are involved in septum formation. The findings from our study highlight the importance of timely endocytosis of cytokinetic enzymes at the division site in safeguarding mitotic spindle integrity during mitotic exit.
Highlights
During mitosis in budding yeast, many cellular processes such as sister chromatid separation and spindle elongation are controlled by the mitotic cyclin-dependent kinase (CDK1) whose activity serves to activate or inactivate its substrates through phosphorylation
The cytokinesis machinery that is required for physical separation of mother-daughter cells during mitosis is highly conserved from yeast to humans
Cytokinesis is achieved via timely delivery of cytokinetic enzymes to the division site that eventually triggers the constriction of acto-myosin ring (AMR)
Summary
During mitosis in budding yeast, many cellular processes such as sister chromatid separation and spindle elongation are controlled by the mitotic cyclin-dependent kinase (CDK1) whose activity serves to activate or inactivate its substrates through phosphorylation (reviewed in [1]). As the cell progresses through mitosis, mitotic CDK1 activity is eventually abolished due to the combinatory effect of mitotic cyclins proteolysis and expression of CDK1 inhibitors. The decline of mitotic CDK1 activity, known as mitotic exit, is a tightly-regulated process involving components that are highly conserved across species. The binding of Cdh1p to APC/C is under the control of a Hippo-like signal transduction cascade known as the Mitotic Exit Network (MEN) comprising of Tem1p (a GTPase), Lte1p (a GTP/GDP exchange factor), Cdc15p (Hippo-like kinase), Cdc5p (Polo-like kinase), Dbf2p/ Dbf20p (Ser/Thr kinase), Mob1p (a kinase), and its ultimate effector Cdc14p (Ser/Thr phosphatase) [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
