Nuclear domains involved in inositol lipid signal transduction

The complexity of inositol lipid signaling system has expanded impressively in recent years. The molecular species involved present an unsuspected heterogeneity we are only just beginning to understand. Furthermore, many polyphosphoinositides are not only the substrates of enzymes which generate second messengers, but act as second messengers by specific interactions with proteins. These interactions occur at different cell sites, such as cell membrane, intracellular vesicles, cytoskeleton, and nucleus, thus modulating the principal cell functions. In this context, the widely documented presence of inositol lipid substrates and of the related enzymes at the nuclear level indicates that a signal transduction system, autonomous with respect to that at the cell membrane, provides the modulation of peculiar functions of the nucleus. The main characteristic of the nuclear organization is the absence of membrane-delimited organelles, although the complex nuclear metabolism is compartmentalized at specific macromolecular domains. Here we report the main evidence of a ordered localization of many of the components of the inositol lipid signaling system at specific nuclear domains. These domains, the interchromatin granules and the perichromatin fibrils, are involved in pre-mRNA transcription and splicing, and are modulated by interaction with the inner nuclear matrix. Co-localization cytochemical methods demonstrate that inositol lipid kinases and phospholipases are located at the same sites through inositol lipid substrate-nuclear protein interactions. Furthermore, the nuclear inositol lipids not only provide second messengers capable of recruiting protein kinases capable of phosphorylating nuclear enzymes, but can directly modulate the chromatin arrangement in order to release the template restrictions and trigger transcriptional activities.