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R E V I E W S
Lasting activity-dependent changes in synaptic strength depend on new protein synthesis and the growth or remodelling of excitatory synapses. The dendritic tree of a typical projection neuron in the adult mammalian brain contains approximately 10,000 dendritic spines, onto each of which is formed a single excitatory synapse. As a discrete structural, physiological and biochemical compartment, dendritic spines afford a necessary degree of autonomy during information processing and storage. The discovery of mRNA, ribosomes and translation factors in dendrites, and even in the dendritic spines themselves, suggested that synapses could be modified directly and perhaps individually through regulation of local protein synthesis1,2.
Although numerous (possibly several hundred) mRNA species are distributed in the dendrites of cultured neurons, far fewer such dendritic mRNAs have been experimentally confirmed in adult non-cultured neurons. TABLE1 lists some of the dendritic mRNAs
for which key regulatory features are known. Different neurons express different sets of dendritic mRNAs, and some transcripts appear to be unique to a specific class of neuron. As the postsynapticdensity (PSD) of excitatory synapses consists of more than 300 different proteins assembled into elaborate complexes, it is not surprising that dendritic mRNAs encode a diverse array of proteins, including neurotransmitter receptors, scaffolding proteins and signal transducing enzymes. More unexpectedly, dendrites also contain mRNA for secre-tory proteins, such as tissue plasminogen activator (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5327&ordinalpos=1&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Web End =tPA ) and matrix metalloproteinase 9 (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4318&ordinalpos=1&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
Web End =MMP9 ).
This Review highlights recent advances in our understanding of the mechanisms of mRNA transport, localization and translation in dendrites. Particular emphasis is placed on the regulation and coordination of these mechanisms, and on the function of dendritic protein synthesis in activity-dependent synaptic plasticity in the adult mammalian brain, using long-term potentiation (LTP) and long-term depression (LTD) as examples.
Transport and localization
That mRNA can distribute into both neuronal axons and dendrites is well established. However, the mechanism by which specific mRNAs are transported is still largely a mystery. What is evident is that the process of mRNA localization in neuronal dendrites is complex, and involves multiple mRNA binding proteins and at least three types of RNA-containing granules: ribonucleoproteinparticles (RNPs), stressgranules (SGs) and processing bodies (PBs)3,4 (BOX1). A model for mRNA transport and localization in neurons is...