How mRNA localization and protein synthesis sites influence dendritic protein distribution and dynamics

In this issue ofNeuron,Fonkeu et al. (2019)present a mathematical model of mRNA and protein synthesis,degradation, diffusion, and trafficking in neuronal dendrites. The model can predict the spatial distributionand temporal dynamics of proteins along dendrites. The authors use the model to account forin situimagingdata of CaMKII⍺mRNA and protein in hippocampal neurons

Statistical Laws of Protein Motion in Neuronal Dendritic Trees

Across their dendritic trees, neurons distribute thousands of protein species that are necessary for maintaining synaptic function and plasticity and that need to be produced continuously and trafficked to their final destination. As each dendritic branchpoint splits the protein flow, increasing branchpoints decreases the total protein number downstream. Consequently, a neuron needs to produce more proteins to maintain a minimal protein number at distal synapses. Combining in vitro experiments and a theoretical framework, we show that proteins that diffuse within the cell plasma membrane are, on average, 35% more effective at reaching downstream locations than proteins that diffuse in the cytoplasm. This advantage emerges from a bias for forward motion at branchpoints when proteins diffuse within the plasma membrane. Using 3D electron microscopy (EM) data, we show that pyramidal branching statistics and the diffusion lengths of common proteins fall into a region that minimizes the overall protein need