F-BAR protein function in cytokinesis: studies of phosphoregulation and disordered domains
Mangione, MariaSanta
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2019-09-13
Abstract
Cytokinesis is the physical separation of two daughter cells. Coordination of cytokinesis with genome duplication and segregation is essential for the viability of all cells. Yeast, amoebas, and animal cells assemble an actin- and myosin-based contractile apparatus called the cytokinetic ring (CR) that mediates plasma membrane ingression and fusion and eventual cell separation. The CR contains additional proteins including membrane anchors, actin-binding proteins, and scaffolds that coordinate the CR with the extracellular environment and other cellular processes. There are many unanswered questions about how these proteins are integrated into a functional unit, how individual proteins are regulated, and how cytokinesis is globally regulated to ensure safe and successful cell division. These studies use the fission yeast Schizosaccharomyces pombe to investigate the regulation and function of a key protein for linking the CR to the plasma membrane, the F-BAR protein Cdc15. Cdc15 binds membrane lipids with its F-BAR domain and interacts with CR proteins via its SH3 domain. Here I establish that the intrinsically disordered region that links these two globular domains is essential and important for Cdc15’s scaffolding functions recruiting the phosphatase calcineurin, maintaining CR integrity during constriction, and interacting with paxillin Pxl1. Both Cdc15 and Pxl1 are phosphorylated primarily in intrinsically disordered regions. I also identify multiple kinases and/or phosphatases that regulate their phospho-status, demonstrating the overlapping regulation that exists to ensure the success of this vital process. Phosphorylation of both proteins regulates their interaction with each other and proper regulation is important for successful cytokinesis. Together this work exemplifies the intricate architecture of the CR and the complex regulation that is required to ensure successful cytokinesis.