Mikhaylova Lab, (formerly) Uni.klinik Hamburg-Eppendorf (UKE); Current Lab, HU Berlin, Germany

In early neuronal development, the majority of glutamatergic synapses are located on dendritic shafts. Following maturation, they are gradually replaced by excitatory spine synapses. In adult pyramidal neurons in hippocampus about 10% of glutamatergic synapses are still located on the shaft, in the cortex this number can reach up to 30%. In contrast to spine synapses, there is much less known about their structure and function. In ongoing work, we are addressing the stability and plasticity of shaft synapses, testing their role in synaptic transmission and performing detailed characterization of the molecular components. Interestingly, we discovered that shaft synapses play an impor-tant role in regulation of dendritic organelle and membrane protein trafficking. We show, that in contrast to inhibitory shaft synapses, the post-synaptic density of the excitatory shaft synapse is surrounded by a dense mesh of F-actin filaments. Using lysosomes as an example, we show that the presence of actin patches has a strong impact on dendritic organelle transport, as lysosomes frequently stall at these locations.

We provide mechanistic insights on this pausing behavior, demonstrating that actin patches form a physical barrier for kinesin-driven cargo. In addition, we identify myosin Va as an active tether which mediates long-term stalling. This correlation between the presence of actin meshes and halting of organelles could be a generalized principle by which synapses control organelle trafficking.

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