How local protein synthesis affects the size of dendritic protein pool

Neurons use a variety of strategies, including local protein synthesis and pre-established protein pools inside dendrites, to maintain the dynamic proteome requirements for appropriate synaptic activity. While certain proteins have local mRNA that allows for on-demand synthesis at the synapse, the vast majority do not. This poses an important question: how can these proteins manage their copy number without boosting the synthesis rate locally?
This study looks into the hypothesis that the amount of the protein pool in dendrites corresponds with the presence or lack of dendritic mRNA for local protein synthesis. Proteins that lack dendritic mRNA synthesis compensate for this constraint by keeping a larger pre-existing pool inside the dendrite, functioning as a "standby" pool, resulting in a larger dendritic pool than the synaptic population. To investigate this hypothesis, we examined well-established protein and mRNA localization profiles reported experimentally in previous studies. In addition, we developed a mathematical model to represent the distribution of neuronal mRNA and proteins within the dendrites and synapses of a neuron.
Our findings validated the hypothesis, indicating a negative relationship between dendritic mRNA and the amount of the pre-existing dendritic protein pool. Simply meaning, proteins without the capacity to synthesize locally had a greater "stand-by" pool within the dendrite than those with local mRNA. To further confirm these findings, we used existing synaptic and dendritic protein imaging data from prior work [1], as well as dendritic mRNA localization data from [2].
These findings provide a unique viewpoint on the mechanisms behind the varied distribution of molecules inside dendrites. The interaction of local protein production and pre-existing dendritic pools is identified as a critical element in generating the dynamic proteome at synapses.