Path to Successful Cytokinesis

When we think of mitosis, the intricate process of DNA replication followed by precise alignment of the duplicated chromosomes and their distribution to the daughter cells comes immediately to mind. However, equally important is the process of cytokinesis by which the remainder of the cell’s contents are equally divided and distributed. In many cell types, a contractile ring (CR) forms around the equator of the dividing cell, defining a plane along which cytokinesis will occur. Constriction of this ring is ultimately responsible for splitting the cell’s contents as the chromosomes move towards their respective newly forming nuclei. Despite considerable research, however, the mechanisms that dictate formation and constriction of the CR remain a mystery. Now, work from Vanderbilt Basic Sciences investigator Kathy Gould and her laboratory shows that the yeast protein Efr3 is intricately involved in CR function in dividing yeast. Previous work had shown that Efr3 works together with a partner protein Ypp1 to form a platform for the phosphatidylinositol-4 kinase Stt4 at the plasma membrane. This enables Stt4 to increase the levels of phosphatidylinositol 4-phosphate (PI(4)P) and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the membrane. (PI(4,5)P2) serves as a binding site for a number of CR-associated proteins, and levels of the phospholipid are elevated in the region of the assembling CR. The investigators showed that deletion of Efr3 results in reduced levels of PI(4)P and (PI(4,5)P2) in the membrane, and although the CR appears to form normally, it slides away from its correct central position during constriction, resulting in two unequally divided daughter cells. Multiple genetic studies showed that Efr3 functions to maintain CR position by a mechanism distinct from that of other proteins known to be important in CR function. Then, further work demonstrated that Myo51, a type V myosin, is required to observe abnormal division in Efr3-deficient cells. The findings suggest that Myo51 exerts perpendicular forces on the CR as it constricts and that Efr3 is required to prevent slipping of the CR away from the center in the presence of these forces. The discovery of these myosin-dependent forces in CR function provides new insight into the process of cytokinesis. The work is published in the Journal of Cell Biology [C. E. Snider et al., (2017) J. Cell Biol., published online August 7, DOI: 10.1083/jcb.201705070].

 

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