Mathematical Biology Seminar

Erik Jorgensen
Biology Department, University of Utah
Wednesday Nov. 25, 2009
3:05pm in LCB 225
Synaptic vesicle acidification is a checkpoint for vesicle fusion.

Abstract: When a synaptic vesicle fuses with the plasma membrane it releases a fixed amount of neurotransmitter. Why? One possibility is that only vesicles that are filled with neurotransmitter are substrates for release. However, mutations in the transporters or biosynthetic enzymes lead to decreases in neurotransmitter release. These data suggest that there is no neurotransmitter checkpoint for vesicle fusion.

Transmitter is loaded into vesicles using secondary active transport, that is, the vacuolar H+-ATPase pumps protons into the vesicle and protons are then exchanged for neurotransmitter. Surprisingly, mutations in the V-ATPase did not decrease the amount of neurotransmitter. Rather, the frequency of the vesicle fusions was reduced. Our results are consistent with an acidification checkpoint whereby only fully acidified synaptic vesicles are competent to fuse. The uniform neurotransmitter content may be controlled not by a direct mechanism that monitors neurotransmitter content in a vesicle, but instead by an indirect mechanism affected by the acidification state of the vesicle.