Dynamin Isoforms Decode Action Potential Firing for Synaptic Vesicle Recycling

Abstract

Background: The molecular mechanism linking variation in presynaptic neuronal activity to vesicle trafficking is unknown. Results: Three isoforms of dynamin, an essential endocytic protein, mediate vesicle reuse, having distinct rate and time constants with physiological action potential frequencies. Conclusion: Dynamin isoforms select appropriate vesicle reuse pathways associated with specific neuronal firing patterns. Significance: Individual dynamin isoforms regulate distinct synaptic vesicle reuse pathways that cover the full range of physiological action potential frequencies.

Kinetic Organization of Ca2+ Signals That Regulate Synaptic Release Efficacy in Sympathetic Neurons

“…Thus, kinetic analysis suggests rapid and slow Ca 21 signals may regulate the specificity of fast and slow endocytosis pathways. In addition, these results suggest that slow Ca 21 signal regulation does not contribute to control of the rapid RRP replenishment rate but does determine the RRP size through RP replenishment activated by a long train of AP firing (Lu et al, 2009;Tanifuji et al, 2013). Ca 21 Entry Regulates SV Availability for the ShortTerm Plasticity.…”

“…This time scale suggests that SVs recycle via molecular sensors for endocytosis. Endocytosis at many synapses requires initiation by Ca 21 /CaM (Wu et al, 2009) and dynamin (Tanifuji et al, 2013) that mediates fission of SVs from the presynaptic terminal membrane (Takei et al, 1995). The precise Ca…”

“…Previously we showed that after depletion of the RRP, the SV pool recovers at two time constants, fast and slow, through dynamin-mediated distinct endocytosis pathways (Lu et al, 2009;Tanifuji et al, 2013). Here, to map Ca 21 specificity onto the fast and slow components, we compared recovery time constant with exponential growth curves fitted to the increase in the mean EPSP amplitudes of 4 seconds (during the fast recovery) and 1-6 minutes (during the slow recovery) after cessation of the AP train.…”

“…Averaged EPSP amplitudes after 4-minute AP trains in control and in the presence of Ca 21 chelators or DMSO were fitted with single exponential growth curves from 0 to 4 seconds or from 1 to 6 minutes using Origin 8. To show clearly the fast recovery rate, the mean value of baseline noise level recording at time 5 0 (,1 mV) was subtracted from mean EPSP amplitudes (Tanifuji et al, 2013).…”

“…In SCG neurons, dynamins 3 and 1 mediate endocytosis with fast and slow latency of their activation after an AP, respectively, while dynamin 2 mediates both modes of endocytosis (Tanifuji et al, 2013 21 has an essential kinetic role in both rapid and slow changes in the RRP size, which can be defined as the number of SVs accessible for exocytosis in response to an AP (Rizzoli and Betz, 2005). Following RRP depletion with high-frequency AP trains, both rapid and slow Ca 21 -dependent regulation mediate recovery with fast (t , 3.4 seconds) and slow (t , 4.4 minutes) kinetics (Fig.…”