Relax? Don't do it!-Linking presynaptic vesicle clustering with mechanical tension.

The release of transmitter-filled vesicles from presynaptic terminals is a key step of neurotransmission. Prior to release, synaptic vesicles get clustered at a specialized patch of the presynaptic membrane, here referred to as the active zone. So far, mainly biochemical regulations at the active zone were regarded as decisive for synaptic vesicle clustering and release. However, using biophysical approaches, a recent paper [Siechen, et al. (2009). Proc. Natl. Acad. Sci. U.S.A. 106, 12611-12616] indicated also that the micromechanical regulations within axon and terminal could be crucial for proper vesicle clustering. The authors demonstrated that the synaptic vesicle accumulations vanished after axotomy but were restored after the application of physical tension. Furthermore, axons seem to be under an intrinsic tension, which could be perceived and tuned by an axon-internal tension sensing mechanism. Therefore, mechanical force could steer vesicle clustering and consequently synapse function. Here, we review this interdisciplinary study of Siechen, et al. [Proc. Natl. Acad. Sci. U.S.A. 106, 12611-12616 (2009)] and discuss the significance of cellular mechanics on synaptic function.