Cellular Immediate-Early Genes in the Nervous System: Genes for All Reasons?

Abstract Neurotransmitters, polypeptide growth factors and hormones operate through multiple signaling pathways to elicit the induction of a class of genes referred to as cellular immediate-early genes. This gene class consists primarily of genes encoding transcription factors, such as c- fos and c- jun , that are thought to couple transient ligand–receptor interactions to a complex cellular response that involves the regulation of gene expression. However, several lines of evidence indicate that the cellular immediate-early gene class may also contain genes whose protein products function in other aspects of cellular physiology, including growth and signal transduction. Here we will discuss the properties and makeup of the cellular immediate-early gene class and suggest how this may represent an integrated biological response to stimulation. In the mammalian central nervous system (CNS), neurons undergo profound changes in excitability, synaptic organization and cellular phenotype in response to brief periods of excitation. Although a considerable amount of information has been gathered regarding the short-term cellular changes that occur following stimulation, the molecular mechanisms whereby transient ligand–receptor interactions are converted into long-term changes in neuronal phenotype and behavior still largely remain to be elucidated. However, a number of advances in the field of cancer cell biology have pointed to some of the molecular details of processes that might link an extracellular stimulus to alterations in gene expression. One of the most prominent cellular events to occur upon stimulation is the rapid and transient induction of a number of cellular immediate-early (cIE) genes. 48 These genes predominantly encode nuclear proteins such as the transcription factors Fos and Jun. Thus, genes of the cIE class have been viewed as components of signaling pathways that initiate programs of adaptive change by regulating gene transcription. Much of the concept of immediate-early genes has been derived from studies of c- fos and c- jun. However, these are by no means the only members of this gene class and an overemphasis of their properties and biology has led some to take an overly narrow view of the cIE response. Therefore, this review will examine the composition of the cIE gene class expressed in the CNS and will consider whether genes encoding non-nuclear signaling molecules contribute to the immediate-early response.