Vault ribonucleoprotein particles and the central mass of the nuclear pore complex

Nuclear pore complexes (NPCs) are macromolecular pores that span the nuclear envelope and undergo conformational changes in response to changes in cisternal calcium levels. Depletion of cisternal calcium leads to the appearance of a mass within the pore. The identity and role of this central mass remain unknown, although some studies suggest they are vault complexes. Vault complexes are 13 MDa ribonucleoproteins found in the cytoplasm and recently in the nuclei of some species, suggesting that they associate with NPCs to cross the nuclear envelope. Using Forster resonance energy transfer (FRET) measurements between labeled vaults and NPCs, we find significant energy transfer suggesting that vaults and NPCs are closely associated at the nuclear envelope. This is supported by high-resolution electron microscopy measurements revealing significant spatial correlations between gold-labeled vaults and NPCs. As the location of the central mass in the NPC is dependent on cisternal calcium levels, FRET signals under conditions of varying cisternal calcium were also measured and shown to undergo significant changes. Together, these findings suggest that the central mass observed in NPCs may be, at least in part, due to the presence of vaults in the pore. Possible roles in cyto-nuclear trafficking are discussed.