Vaults are large cytoplasmic ribonucleoprotein particles that possess a distinct barrel-shaped morphology. Vaults have a mass of 13 million daltons and are composed of four proteins and a small RNA. Vaults are found in most if not all eukaryotic organisms including the lower eukaryote Dictyostelium discoideum. The ubiquitous distribution of these structures and the strong conservation of their morphology and composition suggest that vault function is essential. Although vaults are largely cytoplasmic, a subpopulation of vaults has been localized to the nuclear membrane at nuclear pore complexes (NPCs). This finding, coupled with vault shape, size and symmetry suggests that vaults may interact with the NPC. The discovery of vaults in Dictyostelium has lead to a molecular approach toward elucidation of vault function in this organism. cDNAs for the two major Dictyostelium vault proteins (MVPalpha and MVPbeta) will be cloned and used to construct gene replacement plasmids. Vault proteins will be ablated or truncated in Dictyostelium by gene targeting and double homologous recombination in order to produce cell lines devoid of vault function. We will examine important features of cellular metabolism and physiology in these mutant lines to determine the cellular functions in which vaults play a role. The recent availability of a cDNA for the rat major vault protein has allowed the design of a PCR strategy for identifying a similar protein in yeast. Once identified, the yeast AM gene will be cloned, sequenced and used to determine if yeast contain vaults and if these structures are essential to yeast growth and survival.
| Slesina, Marco; Inman, Elisabeth M; Moore, Ann E et al. (2006) Movement of vault particles visualized by GFP-tagged major vault protein. Cell Tissue Res 324:403-10 |
| Emre, Nil; Raval-Fernandes, Sujna; Kickhoefer, Valerie A et al. (2004) Analysis of MVP and VPARP promoters indicates a role for chromatin remodeling in the regulation of MVP. Biochim Biophys Acta 1678:33-46 |
| Kickhoefer, Valerie A; Poderycki, Michael J; Chan, Edward K L et al. (2002) The La RNA-binding protein interacts with the vault RNA and is a vault-associated protein. J Biol Chem 277:41282-6 |
| Kickhoefer, V A; Liu, Y; Kong, L B et al. (2001) The Telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle. J Cell Biol 152:157-64 |
| Stephen, A G; Raval-Fernandes, S; Huynh, T et al. (2001) Assembly of vault-like particles in insect cells expressing only the major vault protein. J Biol Chem 276:23217-20 |
| Siva, A C; Raval-Fernandes, S; Stephen, A G et al. (2001) Up-regulation of vaults may be necessary but not sufficient for multidrug resistance. Int J Cancer 92:195-202 |
| Schroeijers, A B; Siva, A C; Scheffer, G L et al. (2000) The Mr 193,000 vault protein is up-regulated in multidrug-resistant cancer cell lines. Cancer Res 60:1104-10 |
| Kong, L B; Siva, A C; Kickhoefer, V A et al. (2000) RNA location and modeling of a WD40 repeat domain within the vault. RNA 6:890-900 |
| Kickhoefer, V A; Siva, A C; Kedersha, N L et al. (1999) The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase. J Cell Biol 146:917-28 |
| Kickhoefer, V A; Stephen, A G; Harrington, L et al. (1999) Vaults and telomerase share a common subunit, TEP1. J Biol Chem 274:32712-7 |
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