RT Journal Article
SR Electronic
T1 <em>Highwire</em> Function at the <em>Drosophila</em> Neuromuscular Junction: Spatial, Structural, and Temporal Requirements
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9557
OP 9566
DO 10.1523/JNEUROSCI.2532-05.2005
VO 25
IS 42
A1 Wu, Chunlai
A1 Wairkar, Yogesh P.
A1 Collins, Catherine A.
A1 DiAntonio, Aaron
YR 2005
UL http://www.jneurosci.org/content/25/42/9557.abstract
AB Highwire is a huge, evolutionarily conserved protein that is required to restrain synaptic growth and promote synaptic transmission at the Drosophila neuromuscular junction. Current models of highwire function suggest that it may act as a ubiquitin ligase to regulate synaptic development. However, it is not known in which cells highwire functions, whether its putative ligase domain is required for function, or whether highwire regulates the synapse during development or alternatively sets cell fate in the embryo. We performed a series of transgenic rescue experiments to test the spatial, structural, and temporal requirements for highwire function. We find that presynaptic activity of highwire is both necessary and sufficient to regulate both synapse morphology and physiology. The Highwire RING domain, which is postulated to function as an E3 ubiquitin ligase, is required for highwire function. In addition, highwire acts throughout larval development to regulate synaptic morphology and function. Finally, we show that the morphological and physiological phenotypes of highwire mutants have different dosage and temporal requirements for highwire, demonstrating that highwire may independently regulate the molecular pathways controlling synaptic growth and function.