Membrane proteins are more efficient in reaching distal dendrites than soluble proteins

Proteins are the essential substrate of learning and memory. However, while memories can last a lifetime, proteins are relatively short-lived molecules that need to be replenished every couple of days. This represents a huge logistical challenge for over 85 billion neurons in the brain: billions of proteins must be continuously produced, shipped, routed and installed in the right place in the cell. Scientists from the Max Planck Institute for Brain Research have now addressed a bottleneck in the protein trafficking system, dendritic branch points. They find that protein surface diffusion is more effective at delivering proteins to distal dendritic sites than cytoplasmic diffusion.

“Dendritic arborization of neurons is one of the fascinating features that have evolved to increase the complexity of the interactions between neurons. However, a more complex dendritic tree also increases the difficulty of the logistical task of delivering proteins to each part of the neuron. “says Tatjana Tchumatchenko, head of the research group at the Max Planck Institute for Brain Research who led the study.

Neurons distribute thousands of different protein species, necessary to maintain synaptic function and plasticity through their dendritic arbor. However, most proteins are synthesized hundreds of microns away from distal synapses in the soma (its cell body). How do proteins reach distal sites? “In this study, we focused on passive transport of proteins which corresponds to free diffusion. Unlike active transport via molecular motors, diffusion is energetically cheap. However, there is a disadvantage: passive transport is slow and slow. non-directional “, explains Fabio Sartori, graduate student in the Tchumatchenko group and lead author of the new study.

Surface diffusion is more effective

What happens when proteins encounter dendritic branch points? The branch points are like intersections for traffic, some of the proteins will turn to the right, others to the left. Car intersections can be traffic bottlenecks. Likewise, the greater the number of branching points the proteins encounter on their journey, the less the total number of proteins downstream. Consequently, a neuron needs to produce more proteins to maintain a minimum number of proteins in the distal synapses. “We used the experimental data provided by our collaborators and developed a new computational framework to compare two classes of proteins, based on their” transport medium “: soluble proteins that diffuse in the cytoplasm and membrane proteins”, Sartori says. “Interestingly, we find that surface diffusion is on average 35 percent more effective than cytoplasmic diffusion at delivering proteins to downstream locations.

Each protein has a typical distance that it can cover during diffusion, this is its diffusion length. The higher this value, the more proteins will reach the distal dendrites. If a dendritic branch has a large radius, it can carry more proteins. The combination of two factors, the amplitude (or radii) of the dendrites and the distance that proteins can travel, determines the number of proteins a neuron must produce to supply all the synapses. Sartori and colleagues found that by optimizing dendritic rays, a neuron can reduce the total number of proteins and therefore the cost of protein synthesis by several orders of magnitude. “Our results suggest that neuronal dendritic morphologies play a key role in shaping neuronal function and reflect optimization strategies and constraints imposed by protein trafficking,” concludes Tchumatchenko.