There is a mysterious structure lurking in your cells' cytoplasm. These giant ribonucleoprotein particles (RNA plus protein) are known as vaults because part of their structure, highlighted by staining, reminded researcher Nancy Kedersha of vaulted church ceilings. They are found in all eukaryotic cells and are very common in cancer cells and multi-drug resistant cancer cells, however researchers don't know much about their function. They are`wonderful structures', says Kathy Suprenant at the University of Kansas,describing vaults as being barrel-shaped with a drawn-in waist, and with caps on the ends. Intrigued by vaults' presence in the cells she was studying,Suprenant set out to find out more about them(p. 946).

First Suprenant wanted to see if vaults had any molecular relatives. With bioinformatics experts Jianwen Fang and Gerald Lushington, Suprenant used a sequence alignment tool called BLAST which searches protein sequence databases for similarities or matches between sequences. She chose a repeated sequence of amino acids close to the end of the vault protein and found that this sequence in the vault protein was very similar to the sequence of TELA, a bacterial protein family.

The best match from their search was a TELA protein called TelA from the bacteria Rhodobacter sphaeroides. Since the structure of the vault protein had already been well described the team next characterised the structure of Rhodobacter's TelA protein. Using a computer program which predicted how protein sequences might fold, they found that the TelA protein could fold in the same way as the vault protein, which suggested that they were related in function. The team knew that TelA proteins in Rhodobacter are involved in resistance to the environmental toxin tellurite, which is an oxyanion – a negatively charged ion containing oxygen – of the metalloid tellurium. Could vault proteins in mammalian cells also be involved in resistance to tellurite and similar toxins?

To find out, the team used human cells in culture and added tellurite to the culture medium. Using fluorescent antibodies that tagged the vault proteins, allowing them to see where they were in the cell, Suprenant and student Nathan Bloom found that adding tellurite caused vaults to migrate from their position in the cells' cytoplasm to the cell surface, collecting together and forming aggregates called vaultosomes. This response wasn't unique to tellurite, and also occurred in response to other related oxyanions such as arsenite and vanadate. Since vaultosomes were forming in response these toxic anions which stress the cell, the team wondered if vaultosomes formed independently of other known stress responses. Exposing the cells to arsenite, they found that vaultosomes formed independently of RNA-containing stress response particles and did not congregate with them. When they looked at aggresomes, complexes of proteins that form when the cell's ability to clean up misformed proteins is overwhelmed, the team found that vaultosomes did not congregate with aggresomes, either. These results suggested that vaultosome formation may be a unique response to stress.

The abundance of vaults in cancer cells and drug-resistant cancer cells may be part of this unique cellular stress response. In the future Suprenant hopes to determine whether vaults are necessary or sufficient for tellurite and toxic anion resistance. `We need to know a million more things about them,'she says.

Suprenant, K. A., Bloom, N., Fang, J. and Lushington, G.(
). The major vault protein is related to the toxic anion resistance protein (TelA) family.
J. Exp. Biol.