Protein synthesis at synaptic sites on dendrites

Reeve-Irvine Research Center and Departments of Anatomy/Neurobiology and Neurobiology and Behavior, College of Medicine, University of California at Irvine, Irvine, California 92697, USA.
Annual Review of Neuroscience (Impact Factor: 19.32). 02/2001; 24(1):299-325. DOI: 10.1146/annurev.neuro.24.1.299
Source: PubMed


Studies over the past 20 years have revealed that gene expression in neurons is carried out by a distributed network of translational machinery. One component of this network is localized in dendrites, where polyribosomes and associated membranous elements are positioned beneath synapses and translate a particular population of dendritic mRNAs. The localization of translation machinery and mRNAs at synapses endows individual synapses with the capability to independently control synaptic strength through the local synthesis of proteins. The present review discusses recent studies linking synaptic plasticity to dendritic protein synthesis and mRNA trafficking and considers how these processes are regulated. We summarize recent information about how synaptic signaling is coupled to local translation and to the delivery of newly transcribed mRNAs to activated synaptic sites and how local translation may play a role in activity-dependent synaptic modification.

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    • "Classic examples that illustrate the importance of local translational regulation in polarized eukaryotic cells include the translation at the cell periphery of fibroblasts during migration, within axonal growth cones of Xenopus retinal ganglion cells during axon guidance, and in the dendritic compartment of primary hippocampal neurons in synaptic plasticity (Jung et al., 2014). The latter has gained significant attention as the local production of synaptic proteins posits an elegant mechanism to explain how individual dendritic branches or even single synapses are modified locally in response to local stimulation (Steward and Schuman, 2001). Indeed, local translation within dendrites appears to be required for at least some forms of synaptic plasticity, particularly BDNF-mediated synaptic facilitation and mGluR-dependent long-term depression (Huber et al., 2000; Kang and Schuman, 1996). "
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    ABSTRACT: The vast majority of the mammalian genome is transcribed, generating a wealth of transcripts that do not have protein-coding potential. These non-coding RNAs (ncRNAs) have emerged as major mediators of compartmentalized gene expression with many important regulatory functions, and are therefore at the focus of biological research in many cellular systems. The expression of ncRNAs is particularly multifaceted in neurons, as they seem to be expressed in a highly cell-type and activity-dependent manner. Specific subclasses of ncRNAs, especially microRNAs (miRNAs), were implicated in the local regulation of mRNA translation in neuronal dendrites, a process of compartmentalized gene expression that is engaged during synaptic plasticity. Recent discoveries point towards a widespread involvement of ncRNA families in local translation, including less abundant small RNAs (PIWI-interacting RNAs (piRNAs), endogenous small interfering RNAs (endo-siRNAs)) and long ncRNAs (circular RNAs (circRNAs), long intergenic ncRNAs (lincRNAs)). The mechanisms underlying the dendritic transport and the regulatory function of ncRNAs in response to neuronal activity are being elucidated. The emerging picture is an intricate crosstalk between different ncRNA families, mRNAs and RNA-binding proteins (RBPs) that synergistically fine-tune the local dendritic proteome in an activity-dependent manner. Copyright © 2015 Elsevier GmbH. All rights reserved.
    European journal of cell biology 06/2015; 94(7-9). DOI:10.1016/j.ejcb.2015.05.011 · 3.83 Impact Factor
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    • "Chain et al., 1999) developed a scenario that presumes that degradation frees protein synthesis from its endogenous presynaptic and postsynaptic 'negative' suppressor proteins, a widely held hypothesis (Willeumier et al., 2006; Mabb and Ehlers, 2010; Fioravante and Byrne, 2011; Khoutorsky et al., 2013), and thereby unmasks the action of the positive proteins (see also Dong et al., 2014; Wang et al., 2014). The possible roles for the newly synthesized proteins include replacing degraded proteins, increasing the levels of existing proteins, or expressing novel forms of proteins (Steward and Schuman, 2001). On the contrary, protein turnover is activity dependent in the sense that the activity can either suppress or increase the turnover of some kinds of proteins in dendritic spines (e.g., actin: Star et al., 2002 and spectrin: Vanderklish et al., 1995) via, for example, a cytosolic Ca 2+ -mediated truncation by proteases (Vanderklish et al., 1995, 2000; Bi et al., 1998; Ehlers, 2000, 2003). "
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    ABSTRACT: Long-term potentiation (LTP) remains the most widely accepted model for learning and memory. In accordance with this belief, the temporal differentiation of LTP into early and late phases is accepted as reflecting the differentiation of short-term and long-term memory. Moreover, during the past 30 years, protein synthesis inhibitors have been used to separate the early, protein synthesis-independent (E-LTP) phase and the late, protein synthesis-dependent (L-LTP) phase. However, the role of these proteins has not been formally identified. Additionally, several reports failed to show an effect of protein synthesis inhibitors on LTP. In this review, a detailed analysis of extensive behavioral and electrophysiological data reveals that the presumed correspondence of LTP temporal phases to memory phases is neither experimentally nor theoretically consistent. Moreover, an overview of the time courses of E-LTP in hippocampal slices reveals a wide variability ranging from <1 h to more than 5 h. The existence of all these conflictual findings should lead to a new vision of LTP. We believe that the E-LTP vs. L-LTP distinction, established with protein synthesis inhibitor studies, reflects a false dichotomy. We suggest that the duration of LTP and its dependency on protein synthesis are related to the availability of a set of proteins at synapses and not to the de novo synthesis of plasticity-related proteins. This availability is determined by protein turnover kinetics, which is regulated by previous and ongoing electrical activities and by energy store availability.
    Reviews in the neurosciences 05/2015; DOI:10.1515/revneuro-2014-0072 · 3.33 Impact Factor
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    • "Such a process seems too slow to account for a role of protein synthesis in short-term memory. However, activity dependent translation of preexisting mRNA can occur locally in the dendrites (Job and Eberwine 2001; Steward and Schuman 2001) within 5 min to 30 min (Ouyang et al. 1999; Tsokas et al. 2005). This quick time course is consistent with the observed short-term memory impairment and might explain why systemic injections of anisomycin after the training, which might not be quick enough to block the translation of preexisting mRNA, do not impair short-term memory (Bourtchouladze et al. 1998). "
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