Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 42, Pages 9557-9566Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2532-05.2005
Keywords
highwire; synaptogenesis; synaptic transmission; ubiquitin ligase; neuromuscular junction; Drosophila
Categories
Funding
- NINDS NIH HHS [NS043171, R01 NS043171] Funding Source: Medline
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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.
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