How mRNA Localization and Protein Synthesis Sites Influence Dendritic Protein Distribution and Dynamics

Abstract

Proteins drive the function of neuronal synapses. The synapses are distributed throughout the dendritic arbor, often hundreds of micrometers away from the soma. It is still unclear how somatic and dendritic sources of proteins shape protein distribution and respectively contribute to local protein changes during synaptic plasticity. Here, we present a unique computational framework describing for a given protein species the dendritic distribution of the mRNA and the corresponding protein in a dendrite. Using CaMKIIα as a test case, our model reveals the key role active transport plays in the maintenance of dendritic mRNA and protein levels and predicts the short and long timescales of protein dynamics. Our model reveals the fundamental role of mRNA localization and dendritic mRNA translation in synaptic maintenance and plasticity in distal compartments. We developed a web application for neuroscientists to explore the dynamics of the mRNA or protein of interest.

Keywords: computational model; dendrites; dendritic dynamics; local translation; neuron; protein dynamics; synaptic plasticity.