Intracellular Signaling

Interactions between cells in the nervous system are bidirectional and involve a large number of chemical signals. These interactions occur via receptors located at presynaptic terminals, postsynaptic processes, or at a distance. Activation of membrane receptors by neurotransmitters, growth factors, cytokines, or other extracellular signals triggers downstream intracellular signaling pathways that affect a wide range of cellular functions. The final common mechanism is regulation of the state of phosphorylation of multiple crucial proteins in membranes, cytosol, cytoskeleton, and nucleus. The coupling between extracellular signals and these intracellular responses depends on transduction pathways that include G proteins that function as molecular switches; second messenger molecules such as cyclic nucleotides and phosphatidylinositol metabolites; intracellular calcium transients; and activation of protein kinases and phosphatases. Alterations of these fundamental cellular mechanisms provide the bases for a large number of disorders of the nervous system as well as potential therapeutic targets.