Cell division is one of the most fundamental processes of life, conserved across all kingdoms. Over the last decades, scientists have identified many of the components involved in cell division in both bacterial and animal cells. However, how these components work together to divide the cell has remained largely unknown, most particularly in bacteria, which lack the canonical molecular motors used to drive this process in most eukaryotic cells. In bacteria, a ring composed of actin and tubulin homologs forms a ring around the site of future division. The actual cell division process, or cytokinesis, occurs when this ring constricts, while the enzymes associated with this ring build a new cell wall that cleaves the bacteria in half.
A recently published study in Science (PDF) gives new mechanistic insight into this essential process. In a highly collaborative effort, Alexandre Bisson Filho and Georgia Squyres in the Garner lab at Harvard worked with Yen Pang-Hsu and Erkin Kuru in the Brun and VanNieuwenhze labs IU Bloomington, Calum Jukes in the Holden lab at Newcastle University, and Fabai Wu in Cees Dekker lab at Delft University. In regards to this multi lab effort, Ethan Garner said “This collaboration was amazing. I feel that we really did science right in this case, where we reached out to other groups that we working the same problem so that we could synergize, rather than complete”.
They began by examining the motion of FtsZ, a cytoskeletal filament that is required for cytokinesis in bacteria and is distantly related to the tubulin cytoskeletal protein found in eukaryotic cells. Using high-resolution microscopy techniques, they found that FtsZ filaments move around the division site, traveling around the division ring. Cell wall synthesis enzymes ride on these filaments, building new cell wall as they travel along the division site. This causes the cell wall to be synthesized in discrete sites that travel around the division site during cytokinesis, a process which they were able to observe directly by using dyes that label the bacterial cell wall. This shows that the motion of FtsZ is directly responsible for coordinating cell wall synthesis, organizing it in space and time during cytokinesis.
Bacillus subtilis cells during cytokinesis, with FtsZ fluorescently labeled. FtsZ forms a ring-like structure at the division site that constricts as the cells divide. (500x speed).
Using a variety of experimental techniques, they were able to speed up or slow down how fast FtsZ rotated around the cell. Strikingly, they found that the speed of FtsZ filament motion controls the amount of cell wall that is produced at the division site, and determines how fast the cell can divide. When FtsZ moves more rapidly, cell wall is produced more quickly, and cytokinesis happens faster.
Together, these results revealed that the organization of cell wall synthesis by moving FtsZ filaments is an essential part of the cell division process in bacteria. Furthermore, this finding introduces a new view of bacterial cell division. Previously, the cytoskeleton was thought to serve as a static scaffold, recruiting other molecules and perhaps exerting some local force to divide the cell. This new work demonstrates that all the components of cell division are in constant, controlled motion around the division site, orchestrated by the fundamental dynamics of cytoskeletal filaments. This is a striking example of the versatility of cytoskeletal filaments, which are also used in eukaryotic cell division but used in an entirely different way in bacteria.
by Alexandre Bisson, Georgia Squyres and Ethan Garner
Science (PDF)
