Neurotransmission is a form of cellular communication that is truly astounding in its speed, efficiency of coupling electrical depolarization to molecular events, and ability to respond to changes in frequency of electrical stimulation without compromising the rhythm of neurotransmitter release. The secret to this adaptive feature of neurons may be in the selective use of synaptic vesicle populations: those that are poised for immediate release upon arrival of an action potential, and a """"""""reserve pool"""""""" that is further removed from the presynaptic membrane, not to be used unless trains of stimuli demand their participation. The purpose of this project is to examine the role of actin dynamics in controlling use of this reserve pool. We will begin by assessing the effects of selectively stabilizing or destabilizing actin filaments on mobilization of these vesicles, and then characterize the regulation of dynamic actin reorganization in the nerve terminal by making activity-altering mutations in actin depolymerizing factor (ADF) as well as regulators of ADF activity. Solving the molecular ties between actin dynamics and the synaptic vesicle cycle will be prerequisite to our understanding of neurodegenerative diseases involving defective neurotransmission. ? ?
