Abstract
Local translation of dendritic mRNAs plays an important role in neuronal development and synaptic plasticity. Although several hundred putative dendritic transcripts have been identified in the hippocampus, relatively few have been verified by in situ hybridization and thus remain uncharacterized. One such transcript encodes the protein neuronatin. Neuronatin has been shown to regulate calcium levels in non-neuronal cells such as pancreatic or embryonic stem cells, but its function in mature neurons remains unclear. Here we report that neuronatin is translated in hippocampal dendrites in response to blockade of action potentials and NMDA-receptor dependent synaptic transmission by TTX and APV. Our study also reveals that neuronatin can adjust dendritic calcium levels by regulating intracellular calcium storage. We propose that neuronatin may impact synaptic plasticity by modulating dendritic calcium levels during homeostatic plasticity, thereby potentially regulating neuronal excitability, receptor trafficking, and calcium dependent signaling.
Highlights
Local translation of mRNAs in neuronal dendrites provides a means for rapidly eliciting site-specific changes in protein levels during neuronal development and synaptic plasticity
Localization of neuronatin mRNA and protein in mature hippocampal dendrites To understand the function of NNAT in mature neurons, we first examined NNAT expression in rat hippocampal tissue (P21)
We show that Nnat mRNA is expressed and dendritically translated during homeostatic plasticity in mature hippocampal neurons
Summary
Local translation of mRNAs in neuronal dendrites provides a means for rapidly eliciting site-specific changes in protein levels during neuronal development and synaptic plasticity. Gene expression profiling of isolated dendrites identified as many as 450 putative dendritic mRNAs in the hippocampus [5,6,7,8]. One uncharacterized dendritic mRNA encodes the protein neuronatin (NNAT) which was first identified in embryonic rat brain and subsequently shown to be enriched in isolated dendrites [5,14]. Its levels are highest early in brain development, with the NNATa isoform being expressed at E7–10 and the b isoform appearing at E11–14, during the onset of neurogenesis. Non-neuronal data from pancreatic beta and 3T3-L1 cells shows that NNAT resides in the endoplasmic reticulum (ER) and modulates intracellular Ca2+stores [18,19]
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