Cell division with a twist

Researchers have identified an important event in the enigmatic final step of mammalian cell division: thin spiral fibers may physically "cut" one daughter cell from the other, a team reports this week in linkurl:Science.;http://www.sciencexpress.org.

3D reconstruction of high pressure-frozen cells. Red: microtubules; green: 17 nm diameter filaments.
Image copyright Science/AAAS

The finding sheds new light on a fundamental biological process and could lead to a better understanding of cancer, which can be caused by improper cell division. "It's an impressive paper, creatively done with spectacular microscopy," said linkurl:Stephen Doxsey,;http://www.umassmed.edu/cellbio/faculty/doxsey.cfm who studies cell division at the University of Massachusetts Medical School and was not involved in the study. Though the early stages of cell division are generally well understood, the final stage during cell division when cells split, called abscission, has remained the obscure because it is difficult to assay and visualize. As a result, theories abound about how abscission might occur: perhaps mechanical tearing, two cells simply ripping apart and healing afterward; or it could be vesicle-mediated separation, in which golgi- or endosome-derived vesicles establish new membranes to physically partition the two cells. "It's a fundamental biological question," said linkurl:Daniel Gerlich,;http://www.bc.biol.ethz.ch/people/groups/gerlichd a biochemist at the Swiss Federal Institute of Technology in Zurich and senior author of the study. "Without abscission, a dividing cell would never yield daughter cells that could build a multicellular organism."

3D microscopy of late-stage intercellular bridge, stained with fluorescent phalloidin (green) and anti-α-tubulin antibody (red)
Image copyright Science/AAAS

Gerlich and colleagues examined human HeLa cells in the very final stages of cell division using using three-dimensional live microscopy and electron tomography. They identified 17nm wide filaments -- spiral fibers that form helices wrapping around the narrow bridge where two daughter cells pinch apart, like a string wrapped around a bobbin. The team also identified a factor, called Endosomal Sorting Complex Required for Transport, or ESCRT-III, that localized in the constriction zone and appeared to be required for their formation. The appearance of the fibers "seems to be the penultimate step in abscission, which is exciting," said Doxsey. It remains to be determined, however, how exactly the spiral fibers cut the two daughter cells apart. They could be constricting the intercellular bridge by twisting inward or by shortening over time.Though the spiral helices appear to be required for abscission, the paper does leave open the possibility that other factors previously associated with event, such as vesicles and actin, still contribute earlier in the process, added Doxsey. And future studies are needed to confirm whether the same mechanism applies to other organisms. "We would definitely expect this is conserved at least at the level of vertebrates," said Gerlich, who plans to repeat the study with other animal cells. Guizetti, J., et al., "Cortical Constriction During Abscission Involves Helices of ESCRT-III-Dependent Filaments," Science, doi:10.1126/science.1201847.
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