Big Kids: Concluding Remarks


The aim of our studies is to determine the function of vaults. Since function is frequently dictated by structure, we have numerous ongoing projects detailing the structure of the vault particle by conventional electron microscopy as well as cryo-EM. Recent studies have led to the characterization at the molecular level of many of the core vault components. Examination of the sequenced vRNAs has revealed a striking structural similarity which has lent support to the hypothesis that the vRNA serves a functional role in the vault particle. The details of this contribution to vault function need to be resolved. The vRNA genes have turned out to be interesting and possibly highly regulated. Analysis of major vault proteins from a number of species indicates that the MVPs constitute a new class of proteins, highly related to one another but unrelated to any previously characterized cell proteins.

In dictyostelium, where there are at least 3 MVPs, disruption of two MVPs leads to an altered growth phenotype under nutritional stress. The identification of the high molecular weight vault proteins, p240, as a component of telomerase and p193, as a new PARP. reveals an intriguing complexity in this particle. Although the MVP appears to play a structural role, its upregulation in multi-drug resistant cancer cells is intriguing and supports previous predictions that vaults have a transport function.

Are vaults actively transporting drugs and/or RNA and are they interacting with cellular structures, such as the nuclear pore complex? Answers to these questions will be the basis of future studies of vault function.

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