Significance
Cellular signaling pathways respond to a wide range of stimuli. How signaling circuits are activated without an instructive stimulus and what this is good for are less clear. Combining theoretical and experimental approaches, we show that curvature-sensing proteins stabilize stochastic membrane deformations to nucleate a self-organizing actin-regulatory signaling circuit. In neurons, these signaling hubs control the initiation of exploratory filopodia that sample the cell vicinity for appropriate synaptic partners. The extent and diversity of proteins capable of forming self-organizing circuits at stochastically deformed membranes indicates a general signaling mechanism.
The presynaptic compartment of the chemical synapse is a small, yet extremely complex structure. Considering its size, most methods of optical microscopy are not able to resolve its nanoarchitecture and dynamics. Thus, its ultrastructure could only be studied by electron microscopy. In the last decade, new methods of optical superresolution microscopy have emerged allowing the study of cellular structures and processes at the nanometer scale. While this is a welcome addition to the experimental arsenal, it has necessitated careful analysis and interpretation to ensure the data obtained remains artifact-free. In this article we review the application of nanoscopic techniques to the study of the synapse and the progress made over the last decade with a particular focus on the presynapse. We find to our surprise that progress has been limited, calling for imaging techniques and probes that allow dense labeling, multiplexing, longer imaging times, higher temporal resolution, while at least maintaining the spatial resolution achieved thus far.
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