Topology of inositol lipid signal transduction in the nucleus

An increasing body of evidence shows that many of the key inositol lipids a nd enzymes responsible for their metabolism reside in nuclei. Moreover, the association of the nuclear phosphoinositide cycle with progression through the cell cycle and commitment toward differentiation has built a wider pic ture or the implications of phosphoinositides in the control of nuclear fun ctions. This article reviews a central aspect of inositide nuclear signalin g, i.e., the spatial organization of the signaling system within the nucleu s in relationship to the nuclear organization in functional domains. Most o f the evidence obtained with a variety of confocal and electron microscopy immunocytochemical techniques indicates that the phosphoinositides, the enz ymes required for their synthesis and hydrolysis, and the targets of the li pid second messengers are localized at ribonucleoprotein structures involve d in the transcript processing in the interchromatin domains. These finding s demonstrate that nuclear inositol lipids exist in a non-membranous form, linked to structural nuclear proteins of the inner nuclear matrix. They als o suggest that the inositol signaling in the nucleus is completely independ ent of that at the cell surface and that it probably preceded in evolution the systems that are present at the cytoskeletal and cell membrane level. ( C) 1999 Wiley-Liss, inc.