Abstract
Behavior and higher cognition rely on the transfer of information between neurons through specialized contact sites termed synapses. Plasticity of neuronal circuits, a prerequisite to respond to environmental changes, is intrinsically coupled with the nerve cell’s ability to form, structurally modulate or remove synapses. Consequently, the synaptic proteome undergoes dynamic alteration on demand in a spatiotemporally restricted manner. Therefore, proper protein localization at synapses is essential for synaptic function. This process is regulated by: (i) protein transport and recruitment; (ii) local protein synthesis; and (iii) synaptic protein degradation. These processes shape the transmission efficiency of excitatory synapses. Whether and how these processes influence synaptic inhibition is, however, widely unknown. Here, we summarize findings on fundamental regulatory processes that can be extrapolated to inhibitory synapses. In particular, we focus on known aspects of posttranscriptional regulation and protein dynamics of the GABA receptor (GABAR). Finally, we propose that local (co)-translational control mechanism might control transmission of inhibitory synapses.
Highlights
The enormous capacity of the brain to store information and respond to different environmental conditions and challenges crucially rely on underlying mechanisms like synaptic plasticity
Pioneer experiments showed that inhibiting translation blocked the ability of an animal to remember after training (Flexner et al, 1963). In line with this observation, several experiments have shown that strengthening and weakening of synaptic transmission, so called long-term potentiation (LTP) and depression (LTD), respectively, need active translation in a time-dependent manner (Krug et al, 1984; Linden, 1996)
GABA receptor (GABAR) subunits exhibited a trend towards longer 3 -ends when compared with ionotropic glutamate receptor subunits (Figure 1B). These results suggest that GABAR subunit 3 -untranslated region (3 -UTR) have a high(er) potential to be bound by RNA-binding proteins (RBPs)
Summary
The enormous capacity of the brain to store information and respond to different environmental conditions and challenges crucially rely on underlying mechanisms like synaptic plasticity. The spatial selectivity of synapses to undergo changes upon stimulation raised the question of how a cell knows, which synapse is destined for functional and structural remodeling This inspired Frey and Morris (1997) to the idea of ‘‘synaptic tagging.’’ Repetitive activation of synapses, equips such a synapse with a labile molecular ‘‘tag.’’ Eventually, the synaptic tag allows the synapse to recruit newly synthesized proteins. MTOR is essential for proper neuronal function (Costa-Mattioli and Monteggia, 2013; Pernice et al, 2016) It needs to be experimentally verified though whether it might represent an universal synaptic tag or whether it might be specific for a subset of mRNAs. Local protein expression control comprising mRNA transport, local protein synthesis and recruitment of newly synthesized protein remodel the synaptic proteome. The same statistically significant effects were detected when comparing
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