RT Journal Article
SR Electronic
T1 Synaptic Physiology and Ultrastructure in <em>comatose</em>Mutants Define an <em>In Vivo</em> Role for NSF in Neurotransmitter Release
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10241
OP 10249
DO 10.1523/JNEUROSCI.18-24-10241.1998
VO 18
IS 24
A1 Fumiko Kawasaki
A1 Annette M. Mattiuz
A1 Richard W. Ordway
YR 1998
UL http://www.jneurosci.org/content/18/24/10241.abstract
AB N-Ethylmaleimide–sensitive fusion protein (NSF) is a cytosolic protein thought to play a key role in vesicular transport in all eukaryotic cells. Although NSF was proposed to function in the trafficking of synaptic vesicles responsible for neurotransmitter release, only recently have in vivoexperiments begun to reveal a specific function for NSF in this process. Our previous work showed that mutations in aDrosophila NSF gene, dNSF1, are responsible for the temperature-sensitive paralytic phenotype in comatose(comt) mutants. In this study, we perform electrophysiological and ultrastructural analyses in three differentcomt alleles to investigate the function of dNSF1 at native synapses in vivo. Electrophysiological analysis of postsynaptic potentials and currents at adult neuromuscular synapses revealed that in the absence of repetitive stimulation,comt synapses exhibit wild-type neurotransmitter release at restrictive (paralytic) temperatures. In contrast, repetitive stimulation at restrictive temperatures revealed a progressive, activity-dependent reduction in neurotransmitter release incomt but not in wild type. These results indicate that dNSF1 does not participate directly in the fusion of vesicles with the target membrane but rather functions in maintaining the pool of readily releasable vesicles competent for fast calcium-triggered fusion. To define dNSF1 function further, we used transmission electron microscopy to examine the distribution of vesicles within synaptic terminals, and observed a marked accumulation of docked vesicles at restrictive temperatures in comt. Together, the results reported here define a role for dNSF1 in the priming of docked synaptic vesicles for calcium-triggered fusion.