The role of nuclear envelope calcium in modifying nuclear pore complex structure.

Some of the most important trafficking processes in cells involve transport across the nuclear envelope. Whether it is the import of transcription factors or the export of RNA, the only known portal across the double lipid bilayer that forms the nuclear envelope are the macromolecular pores known as nuclear pore complexes (NPCs). Understanding how signals influence the conformation of the NPC is important for testing models of, and perhaps modifying, transport across the nuclear envelope. Here we summarize high-resolution atomic force microscopy studies of NPC structure following manipulation of nuclear envelope calcium stores of nuclei from Xenopus laevis oocytes. The results show that the release of calcium from these stores through the specific activation of inositol 1,4,5-trisphosphate receptors leads to changes in NPC structure observable from both sides of the nuclear envelope. The diameter of the NPC is also sensitive to these calcium stores and increases upon calcium release. Western blot analysis reveals the presence of ryanodine receptors in the nuclear envelope of X. laevis oocytes, although in low abundance. Activation of these calcium channels also leads to the displacement of the central mass and changes in NPC diameter. This change in structure may involve a displacement of the cytoplasmic and nuclear rings of the NPC towards each other, leading to the apparent emergence of the central mass from both sides of the NPC. The changes in conformation and diameter of the NPC may alter cargo access and binding to phenylalanine-glycine repeats lining the pore, thus altering transport.