Neuron-wide RNA transport combines with netrin-mediated local translation to spatially regulate the synaptic proteome.

Sangmok Kim,Kelsey C Martin

doi:10.7554/elife.04158

Abstract

The persistence of experience-dependent changes in brain connectivity requires RNA localization and protein synthesis. Previous studies have demonstrated a role for local translation in altering the structure and function of synapses during synapse formation and experience-dependent synaptic plasticity. In this study, we ask whether in addition to promoting local translation, local stimulation also triggers directed trafficking of RNAs from nucleus to stimulated synapses. Imaging of RNA localization and translation in cultured Aplysia sensory-motor neurons revealed that RNAs were delivered throughout the arbor of the sensory neuron, but that translation was enriched only at sites of synaptic contact and/or synaptic stimulation. Investigation of the mechanisms that trigger local translation revealed a role for calcium-dependent retrograde netrin-1/DCC receptor signaling. Spatially restricting gene expression by regulating local translation rather than by directing the delivery of mRNAs from nucleus to stimulated synapses maximizes the readiness of the entire neuronal arbor to respond to local cues.

Highlights

Synapse formation and long-lasting experience-dependent synaptic plasticity require new RNA and protein synthesis (Kandel, 2001; Kalinovsky and Scheiffele, 2004)
This allowed us to detect the ribosomal protein S6 in distal SNs without any signal from the MN
We have previously reported that local translation is spatially restricted to stimulated synapses during synapse-specific long-term facilitation (LTF) of SN-MN synapses (Wang et al 2009); here, we asked whether local translation is spatially restricted during synapse formation

Summary

Introduction

Synapse formation and long-lasting experience-dependent synaptic plasticity require new RNA and protein synthesis (Kandel, 2001; Kalinovsky and Scheiffele, 2004). Neurons are dramatically polarized and compartmentalized cells, elaborating axonal and dendritic processes that extend long distances and forming thousands of synaptic connections with other neurons. This polarity and compartmentalization poses challenges to the spatial regulation of gene expression during synapse formation and synaptic plasticity: how can the products of gene expression be restricted to specific synapses undergoing activity-dependent changes in structure and function? We considered that the regulated trafficking of stimulus-induced transcripts from nucleus to stimulated synapse would provide a means of directly coupling the requirement for transcription with the requirement for local translation during synapse formation and plasticity. Transcriptional inhibitors block late-phase LTP of rodent

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