Terminal Tension?

Science Signaling  11 Aug 2009:
Vol. 2, Issue 83, pp. ec268
DOI: 10.1126/scisignal.283ec268

Siechen et al. investigated synaptogenesis at the Drosophila neuromuscular synapse and came to the intriguing conclusion that mechanical tension is critical to synaptic vesicle accumulation, as assessed by nerve terminal accumulation of the integral synaptic vesicle protein synaptotagmin-1. Accumulation of synaptic vesicles in the presynaptic nerve terminal is one of the most characteristic features of chemical synapses. Siechen et al. found that when the axons of anterior corner cell motoneurons in living embryos were severed with lasers at about 12 hours of embryogenesis (a stage at which the axon has not yet reached its target muscle), the growth cone from the severed axon still reached its target. However, visualization of the nascent synapse showed decreased accumulation of immunofluorescently labeled synaptotagmin-1 compared with that in nascent synapses made by unsevered neighbors. When axons were severed shortly after synaptogenesis had ensued (at about 14 hours of embryogenesis), nerve terminals subjected to mechanical tension (by pulling on the severed end with a micropipette strongly enough to straighten the axon) for 2 hours showed synaptotagmin-1 accumulation, whereas those that had not been subjected to tension did not. Moreover, pulling on the muscle after synaptogenesis (stretching unsevered axons about 5% of initial length) elicited a substantial increase in synaptotagmin-1 accumulation in the nerve terminal. Analyses of the gaps formed when axons were severed indicated that tension developed after synaptogenesis, and in vivo force measurements with a micro mechanical probe showed that axons that had formed synapses had a resting tension of about 1 nanonewton. The authors conclude that mechanical tension contributes to the accumulation of synaptic vesicles in developing synapses; the mechanisms whereby this signal is conveyed—and what other aspects of synaptogenesis might be affected by tension—remain unclear.

S. Siechen, S. Yang, A. Chiba, T. Saif, Mechanical tension contributes to clustering of neurotransmitter vesicles at presynaptic terminals. Proc. Natl. Acad. Sci. U.S.A. 106, 12611–12616 (2009). [Abstract] [Full Text]