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Journal of Lipid Research, Vol. 45, 1-8, January 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Thematic Review

Nuclear lipids: key signaling effectors in the nervous system and other tissues¹

Robert W. Ledeen² and Gusheng Wu

Department of Neurology and Neurosciences, New Jersey Medical School, The University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103

² To whom correspondence should be addressed. e-mail: ledeenro{at}umdnj.edu

Lipids have long been recognized as quantitatively minor components of the nucleus, where they were initially thought to have little functional importance; but they now command growing interest, with recognition of their diverse signaling and modulating properties in that organelle. This applies to the lipid-poor compartments of the nucleoplasm as well as the relatively lipid-rich nuclear envelope. Phosphoglycerides and sphingomyelin, as the predominant lipids, have attracted the most interest among researchers, but some of the less-abundant lipids such as gangliosides, sphingosine, and sphingosine phosphate are now becoming recognized as functionally important nuclear constituents. Among recent advances in this emerging field are detailed findings on the metabolic enzymes that synthesize and catabolize nuclear lipids; the fact that these are localized primarily within the nucleus itself indicates considerable autonomy with respect to lipid metabolism. Current studies suggest several key processes involving RNA and DNA reactivity that are dependent on these lipid-initiated events. Neural cell nuclei have been the subject of such investigations, with results that closely parallel the more numerous studies on nuclei of extraneural cells.

This review attempts to outline some of the major findings on nuclear lipids of diverse cell types; results with nonneural nuclei will hopefully provide useful guideposts to further studies of neural systems.

Abbreviations: DAG, diacylglycerol; ER, endoplasmic reticulum; INM, inner nuclear membrane; Ins(1,4,5)P₃, inositol trisphosphate; NE, nuclear envelope; NPC, nuclear pore complex; ONM, outer nuclear membrane; PI3K, PtdIns(4,5)P₂ 3-kinase; PL, phospholipid; PLA₂, phospholipase A₂; PLase, phospholipase; PLC, phospholipase C; PLD, phospholipase D; SM, sphingomyelin; SMase, sphingomyelinase

Supplementary key words nuclear envelope • nuclear chromatin • inner nuclear membrane • outer nuclear membrane • nuclear matrix • nuclear phospholipids • nuclear sphingolipids • nuclear glycolipids • phosphoinositide cycle • nuclear gangliosides

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