A new role for IP3 receptors: Ca2+ release during nuclear vesicle fusion

During nuclear assembly, vesicles derived from the mitotic disassembly of the nuclear membranes reform the nuclear envelope. The vesicles first bind to chromosomes, specifically recognize other nuclear vesicles and then fuse to enclose the chromosomes. The proteins that mediate these events are largely unknown. Using reconstituted extracts of Xenopus eggs, we found that nuclear vesicle fusion required elevated (microM) concentrations of free Ca2+ [Sullivan KMC. Busa WB. Wilson KL. (1993) Cell, 73, 1411-1422]. Our data suggest that Ca2+ is released from the vesicle lumen by the activation of IP3 receptors (ligand-gated Ca2+ channels). We propose that the role of IP3 receptors during nuclear assembly may be analogous to that of voltage-gated Ca2+ channels during regulated secretion: to provide a microdomain of high cytosolic Ca2+ that triggers fusion. In this article, we will briefly describe current ideas about nuclear assembly and disassembly, and summarize the evidence that IP3 receptors are required for nuclear vesicle fusion. We will discuss parallels between our results and the role of voltage-gated Ca2+ channels, and Ca2+, in regulated exocytosis. Finally, we will address the question of how IP3 receptors are activated during nuclear vesicle fusion: is there a signal that stimulates IP3 production, or is the channel activated directly?