by Manuel Sánchez and Miguel Vicente
From wheels to turbines, humans have invented a goodly number of machines to perform various mechanical tasks. The same function, e.g., to move a car, can be carried out by motors of different designs. This is also true for cells, where the same function can be carried out by differently designed machines. Just as most cars use a gasoline engine, most microbes and some organelles (e.g., chloroplasts) use the same component, the protein FtsZ, to carry out cell division.
Nevertheless, just as there are cars that use an electric motor and locomotives with a steam engine, some microbes get by without FtsZ and use another system of proteins for their division.
It had already been known that intracellular bacteria, such as the Chlamydia, lack FtsZ. Now, they are joined by an important group of Archaea, the Crenarchaeota, including Sulfolobus acidocaldarius, the species where this was first observed.
What does FtsZ do? This protein resembles tubulin, the eukaryotic cytoskeletal protein that makes microtubules. Microtubules participate in such important processes as vesicle trafficking and chromosomal division during mitosis. During cell division in bacteria and organelles, FtsZ localizes at the center of the cell or organelle where it directs the assembly of the divisome, the division apparatus. (Click here for a movie showing a 3D model of assembly of the bacterial divisome.) FtsZ is an essential protein, meaning that without it bacteria and chloroplasts cannot divide.
Among the Archaea, the euryarchaeotes (the methanogens and halophiles) seem to use FtsZ for cell division, whereas the crenarchaeotes (mostly thermophiles and hyperthermophiles) seem not to. So, how do FtsZ-less Archaea divide?
Division without a Z
How could there not be FtsZ or something similar to it in the Crenarchaeota? A group of researchers at Uppsala University has resolved this quandary. The proteins that make up the division machinery of the FtsZ-less crenarchaeotes are quite different from those found in the Bacteria and the Euryarchaeota. These proteins do not resemble the tubulins, actins, or myosins involved in eukaryotic cell division. Instead, they resemble eukaryotic proteins involved in the formation of endosomal vesicles, starting from the endoplasmic reticulum, and in the release of viruses such as HIV by budding.
Rolf Bernander and collaborators identified three proteins in Sulfolobus acidocaldarius, called CdvA, CdvB, and CdvC. These are made at the correct time, namely as cell division begins. Their genes are found in an operon called cdv (for cellular division). Proteins CdvB and CdvC are homologous to the eukaryotic proteins of the ESCRT-III complex. (ESCRT stands for Endosomal Sorting Complex Required for Transport.) They form vesicles in the lumen of endosomal vesicles by a process know as "concentric rings." (For a review article, click here.) Let's think about this for a moment. As shown in the drawing below, making such vesicles is somewhat analogous to cell division by budding. The third gene, cdvA, encodes a protein that resembles other eukaryotic cytoskeletal proteins that are distinct from tubulin.
The panel on the right represents the phases of cell division in S. acidocaldarius. After the chromosome has replicated and segregated, a constriction is made in the center of the cell. The Cdv proteins become localized in the middle of the cell, suggesting that they may play a role in constriction. On the right, we diagram the process of endosomal vesicle formation during the processing of membrane receptors in eukaryotic cells. Such receptors are internalized via an invagination of the cytoplasmic membrane. This results in a vesicle that then fuses with others, making a larger vesicle termed the endosome. In time, the endosome makes new invaginations, liberating smaller vesicles within it. Here is where the ESCRT-III (stages 1, 2, and 3) act. The result is a large vesicle full of little vesicles, which is known as the multivesicular body. In time, this structure fuses with lysosomes to bring about the destruction of its contents.
The expression of these three Cdv genes in S. acidocaldarius is regulated by a control “checkpoint” so that their synthesis is only induced when chromosome segregation begins. If something goes wrong with DNA replication, for example due to UV irradiation, these proteins are not made and cell division is inhibited. Likewise, these proteins are not made when cell division is blocked due to the halting of growth or due to cell division-inhibiting antibiotics or mutations.
So, how is “division” spelled?
That the crenarchaeotes utilize a conserved eukaryotic mechanism for a different purpose has a number of phylogenetic implications. Looking at the phylogeny of the Archaea, it is thought that the first divergence took place between the Archaea/Eukarya lineage and the Bacteria. Later, the Archaea split into the Euryarchaeota and Crenarchaeota. This suggests that the FtsZ division apparatus is older, but that it may have coexisted with one based on CdvB and CdvC. When the two archaeal branches diverged, the Euryarchaeota retained FtsZ, the Crenarchaeota adapted the other system. Eukaryotes evolved a different cell division mechanism, using the Cdv system for making vesicles. The heir of FtsZ, tubulin, was destined for the cytoskeleton to “carry things,” such as moving chromosomes from one side of the cell to another.
It is interesting that within the prokaryotes, the two division mechanisms appear to be mutually exclusive. On the one hand, we have the FtsZ system used by the Bacteria and Euryarchaea, on the other the Cdv system of the Crenarchaea. Thus, some use an internal combustion engine, others an electric one. But there are also some that work like hybrid cars, using both FtsZ and Cdv proteins: one group of crenarchaeotes (the Thermoproteales) plus one euryarchaeote, Thermoplasma acidophilum. More surprising still, there is a third group of archaea (the Cenarchaeales) that uses neither. Do they use a turbine?
Authors' Note: This article appeared simultaneously in the two blogs administered by each of the authors, in the hope of stimulating the public to visit one or the other to obtain a wider view of the curiosities of these small bugs.