Targeting of mRNAs into Neuronal and Glial Processes: Intracellular and Extracellular Influences

Neurons and macroglia share the common, polarizing, morphological feature of multiple processes extending from a cell body, thereby defining two cellular domains. Frequently, specialized cellular activities occur within these processes, such as the dendrites of neurons and the myelin sheath of oligodendrocytes, which serve to define some of the functions of the cell. As a consequence, molecules involved in carrying out these functions need to be targeted to these domains, and mechanisms must exist for selecting and delivering these molecules to their appropriate locations. One mechanism that is emerging as increasingly important in targeting proteins to distal processes of neural cells is the translocation of the mRNAs encoding those proteins. In this review, we present many examples of such translocated mRNAs in neurons, astrocytes, and oligodendrocytes. There is a growing consensus that four major steps occur in mRNA targeting after transcription and exit of these molecules from the nucleus. These include 1) the assembly of mRNA into an RNA-protein granule, presumably around some translocation signal within the mRNA; 2) transport of the mRNA granule complex to distal sites via the cytoskeleton; 3) anchoring of the granule at the targeting site; and 4) translation of the localized mRNA to generate protein products in situ. It has become increasingly apparent that mRNA translocation is an active process, although many of the components of the translocation apparatus remain to be identified. Recent evidence also indicates that a number of factors can regulate the transport of mRNAs from within and without the cell. These include cell-cell contact, differentiation state, electrical activity, and trophic factors, which seem to exert their influence through signal transduction mechanisms that are only beginning to be defined. NEUROSCIENTIST 4:77-87, 1998