Localization of mRNAs at Synaptic Sites on Dendrites Oswald Steward 1 and Paul Worley 2 1 Introduction It is becoming increasingly clear that an important aspect of gene expression in neurons involves the delivery of mRNAs to particular subcellular domains. Specifically, although the majority of the mRNAs that are expressed by neurons are found only in the neuronal cell body, a select population of mRNAs are transported into dendrites, and certain neurons also transport mRNA into axons. The nature and significance of this RNA targeting is now under intense investigation, and it is clear that mRNA targeting plays a key role in several aspects of neuronal function. The present chapter focuses on one aspect of RNA localization in neurons – the localization of protein synthetic machinery and particular mRNAs at synaptic sites on dendrites. We will briefly summarize what is known about the protein synthetic machinery that is localized at synapses, update the list of mRNAs that have been shown to be present in dendrites, and consider some of the key principles regarding dendritic mRNAs. We will focus especially on recent evidence regarding the mechanisms underlying mRNA sorting, trans- port, and selective localization at synapses as revealed by studies of the imme- diate early gene Arc. Finally, we will consider new information about the role that local translation plays in synaptic function. 2 The Machinery for Translation in Dendrites The story regarding the targeting of mRNAs to dendrites had its roots in the discovery of synapse-associated polyribosome complexes (SPRCs). SPRCs are polyribosomes and associated membranous cisterns that are selectively local- ized beneath postsynaptic sites on the dendrites of CNS neurons (Steward and Levy 1982; Steward 1983; Steward and Fass 1983). Although it had long been known that polyribosomes were present in dendrites, these studies in the early 1980s were the first to note and document the highly selective localization Results and Problems in Cell Differentiation, Vol. 34 D. Richter (Ed.): Cell Polarity and Subcellular RNA Localization © Springer-Verlag Berlin Heidelberg 2001 1 Reeve-Irvine Research Center, Departments of Anatomy/Neurobiology and Neurobiology and Behavior, College of Medicine, University of California at Irvine, Irvine, CA 92697, USA 2 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA