Abstract
Dendritic protein synthesis plays a critical role in several forms of synaptic plasticity, including BDNF (brain-derived neurotrophic factor)-mediated long-term synaptic potentiation (LTP). Dendritic transcripts are typically transported in a repressed state as components of large ribonucleoprotein complexes, and then translated upon stimulation at, or in the vicinity, of activated synapses. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) is a trans-acting factor involved in dendritic mRNA trafficking, but how the distribution of the protein in dendrites is regulated has not been characterized. Here we found that a fraction of hnRNP A2/B1 is present at the synapse under resting conditions in cultured hippocampal neurons. Accordingly, this ribonucleoprotein was detected in free mRNP, monosomal, and polyribosomal fractions obtained from synaptoneurosomes. Neuronal activity and BDNF treatment increased hnRNP A2/B1 protein levels in the cell body and dendritic compartments, and induced the delivery of this protein to synaptic sites. The activity-dependent accumulation of hnRNP A2/B1 at the synapse required, at least in part, the activation of TrkB receptors, presumably by BDNF. This neurotrophin also upregulated the hnRNP A2/B1 mRNA in the soma but was without effect on the abundance of neuritic hnRNP A2/B1 transcripts. These results show that the distribution of hnRNP A2/B1 is regulated by BDNF and by neuronal activity, an effect that may have a role in BDNF-induced synaptic plasticity events.
Highlights
Experience-dependent changes in synapse structure and function are thought to underlie learning and memory formation [1]
Results hnRNP A2/B1 is required for the dendritic localization of mRNAs encoding proteins that are relevant for synaptic plasticity, such as CaMKIIa and Arc [7]
To test if hnRNP A2/B1 is present at the synapse, we analysed the colocalization with the postsynaptic marker PSD95, in cultured hippocampal neurons (Fig. 1A; 1A9)
Summary
Experience-dependent changes in synapse structure and function are thought to underlie learning and memory formation [1] Some of these modifications require activity-dependent transport and translation of dendritic-localized mRNAs, with concomitant local alterations in the proteome [2]. Dendritic mRNAs are usually packaged into large messenger ribonucleoprotein complexes (mRNPs) in the cell body and transported along the microtubule cytoskeleton until they reach their destination During this process, the transcripts are usually kept in a dormant state and translated upon synaptic activation [4]. One of the best described RNA-binding proteins involved in mRNA trafficking is the hnRNP A2/B1, which recognizes a cis-acting element present in the myelin basic protein (MBP) mRNA [5,6]. Given the nature of some of the hnRNP A2/B1associated transcripts, the protein may play a role in long-term synaptic potentiation
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