title: Dendritic mRNA targeting and translation.
abstract: Selective targeting of specific mRNAs into neuronal dendrites and their locally regulated translation at particular cell contact sites contribute to input-specific synaptic plasticity. Thus, individual synapses become decision-making units, which control gene expression in a spatially restricted and nucleus-independent manner. Dendritic targeting of mRNAs is achieved by active, microtubule-dependent transport. For this purpose, mRNAs are packaged into large ribonucleoprotein (RNP) particles containing an array of trans-acting RNA-binding proteins. These are attached to molecular motors, which move their RNP cargo into dendrites. A variety of proteins may be synthesized in dendrites, including signalling and scaffold proteins of the synapse and neurotransmitter receptors. In some cases, such as the alpha subunit of the calcium/calmodulin-dependent protein kinase II (αCaMKII) and the activity-regulated gene of 3.1 kb (Arg3.1, also referred to as activity-regulated cDNA, Arc), their local synthesis at synapses can modulate long-term changes in synaptic efficiency. Local dendritic translation is regulated by several signalling cascades including Akt/mTOR and Erk/MAP kinase pathways, which are triggered by synaptic activity. More recent findings show that miRNAs also play an important role in protein synthesis at synapses. Disruption of local translation control at synapses, as observed in the fragile X syndrome (FXS) and its mouse models and possibly also in autism spectrum disorders, interferes with cognitive abilities in mice and men.
authors.affiliation: University Medical Center Hamburg-Eppendorf, Institute for Human Genetics, Martinistr. 52, 20246 Hamburg, Germany. kindler@uke.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Kindler
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Kreienkamp
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003712:Dendrites / Q000235:genetics* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D013569:Synapses / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D035683:MicroRNAs; D020409:Molecular Motor Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017981:Receptors, Neurotransmitter; C092069:activity regulated cytoskeletal-associated protein; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases