To enter a cell, the bacteria that causes anthrax hijacks cell-surface receptors that usually control cellular orientation during cell division, according to a new study by researchers at the University of Geneva in Switzerland.
In a paper published in Nature Cell Biology (1), the researchers reported that the cell-surface receptor named anthrax toxin receptor 2a (Antxr2a) plays an integral part in embryonic development and is essential to organ and tissue growth. The receptor orients cell division along a specific plane and produces torque on the mitotic spindle, which pulls duplicated chromosomes to opposite hemispheres of the cell during division.
During animal development, cell-division orientation properly organizes tissue architecture and creates needed cellular diversity. The orientation of the mitotic spindle in cells can be controlled through cell-extrinsic factors, physical constrains, or cell-intrinsic cues. The Antxr2 receptor can now be added to these orientation factors.
For example, during embryonic development, embryos become elongated. The direction of this elongation is determined by the orientation of the dividing cells.
“The place where the receptor was located was actually aligned with this direction and you could forecast where the division was going to happen just by looking at this. And we found eventually that not only does it forecast it, but it controls it,” said Gonzalez-Gaitan.
To find out how the receptor worked, the team tested zebrafish during gastrulation, when cells of the epiblast divide along the animal-vegetal embryonic axis. They then used nucleic acid analogs called morpholinos to isolate and study the function of Antxr2a receptor in the zebrafish, the closest homolog of the human Antxr2 receptor.
As a result, the researchers found that the Antxr2a involves an external signal to initiate its division from Wnt planar cell polarity signaling pathway. Wnt proteins bind to the cell membrane, and a layer of actin filament proteins or actin cap is formed along the cell membrane, where the plane of division will occur.
When anthrax is introduced, it activates a molecule called diaphanous that serves to create actin cables. These cables elongate from the membrane to the mitotic spindle poles and are used to pull on those poles to finally bring the mitotic spindle in line with the axis of the embryos.
For now, Gonzalez-Gaitan is interested in studying the role of Wnt pathway and the receptor but believes that the research will help in understanding the way mitosis works for other processes as well.
“This work, has an impact in the field of how oriented mitosis is happening itself, which is very important for many other processes not only in what we looked at,” said Gonzalez-Gaitan.
1. Castanon, I., L. Abrami, L. Holtzer, C. P. Heisenberg, F. G. van der Goot, and M. GonzÃ¡lez-GaitÃ¡n. 2012. Anthrax toxin receptor 2a controls mitotic spindle positioning. Nature Cell Biology advance online publication (December).