Molecular Mechanisms of Phospholipid Signaling Pathways in Mammalian Nerve Cells

In addition to their structural roles, membrane phospholipids are now recognized to function as information-rich signal generators. This is particularly evident from recent demonstrations that plasma membrane phosphatidylinositol-4,5-bisphosphate (PtdInsP2) is hydrolyzed by a surface-receptor-regulated phospholipase C to produce two molecules with intracellular activities, inositol-1,4,5-trisphosphate (Ins[1,4,5]P3) and diacylglycerol (DAG) (Berridge 1987). The intracellular mediators Ins(1,4,5)P3 and DAG can be regarded as authentic second messengers, comparable to the cyclic nucleotides, in that they function as chemical relays to downstream responses: the discharge of intracellular calcium (Berridge and Irvine 1984) and the activation of membrane-associated protein kinase C (PKC) (Nishizuka 1984), respectively. These events, in turn, are points of amplification and cell-specific diversification in the subsequent activation sequence. Little is known of how particular receptor inputs can generate distinctive responses or of how differentiated cell types modify the receptor-coupled cascade for distinct functional purposes. Accordingly, the detailed analysis of the gene products and...