Finding Centralspindlin

In this paper, Mishima, Kaitna, and Glotzer reported the discovery and characterization of a widely conserved tetrameric protein complex that they dubbed centralspindlin. Using an impressive combination of in vitro biochemistry and in vivo genetics, and including work in both C. elegans and mammalian cell culture, they showed that centralspindlin functions as a complex—not just as individual components—and is required for assembly of the central mitotic spindle and for cytokinesis. We also learned that centralspindlin contains two copies each of a RhoGAP and a kinesin 6 family member (CYK-4 and ZEN-4 in C. elegans; MgcRacGAP and MKLP1 in vertebrates), where the protein-protein interaction domains lie, and that centralspindlin bundles microtubules in vitro. This paper firmly established C. elegans as an important model system for investigating the fundamental cellular process of cytokinesis and laid the foundation for many subsequent studies that have provided substantial mechanistic insight into how the mitotic spindle interacts with and regulates furrow formation during cytokinesis.This PaperPick refers to “Central Spindle Assembly and Cytokinesis Require a Kinesin-like Protein/RhoGAP Complex with Microtubule Bundling Activity” by M. Mishima, S. Kaitna, and M. Glotzer, published in January 2002.The Ins and Outs of CentralspindlinMichael Glotzer takes us on a personal tour of the paper from his group that first described centralspindlin and discusses how our understanding of this complex has developed from there