Abstract
The heparan sulfate proteoglycan (HSPG) Syndecan (Sdc) is a crucial regulator of synapse development and growth in both vertebrates and invertebrates. In Drosophila, Sdc binds via its extracellular heparan sulfate (HS) sidechains to the receptor protein tyrosine phosphatase LAR to promote the morphological growth of the neuromuscular junction (NMJ). To date, however, little else is known about the molecular mechanisms by which Sdc functions to promote synapse growth. Here we show that all detectable Sdc found at the NMJ is provided by the muscle, strongly suggesting a post-synaptic role for Sdc. We also show that both the cytoplasmic and extracellular domains of Sdc are required to promote synapse growth or to rescue Sdc loss of function. We report the results of a yeast two-hybrid screen using the cytoplasmic domains of Sdc as bait, and identify several novel candidate binding partners for the cytoplasmic domains of Sdc. Together, these studies provide new insight into the mechanism of Sdc function at the NMJ, and provide enticing future directions for further exploring how Sdc promotes synapse growth.
Highlights
During synapse development, an incoming neuronal growth cone transforms from a highly motile chemosensory structure into a pre-synaptic terminus, while the post-synaptic cell assembles the machinery required for the detection of neurotransmitter
Postsynaptic expression of Sdc RNAi caused a significant 15% reduction in synapse size (p < .01 n = 34) whereas presynaptic expression of this same construct had no effect on synapse size (p > .05 n = 29; Fig 1G), indicating that postsynaptic Sdc is required for proper synapse growth
In this study we demonstrate that Drosophila Sdc is localized to the neuromuscular junction (NMJ) through postsynaptic expression, and that both the cytoplasmic domains and the extracellular domains are required for Sdc’s ability to promote synapse growth
Summary
An incoming neuronal growth cone transforms from a highly motile chemosensory structure into a pre-synaptic terminus, while the post-synaptic cell assembles the machinery required for the detection of neurotransmitter. At the neuromuscular junction (NMJ) synaptogenesis requires both forward and retrograde signaling between the presynaptic neuron and the postsynaptic muscle, and results in the formation of an exquisitely sensitive structure that translates incoming information in the form of action potentials into the contraction of muscle tissue. Following the initial phases of synapse formation, the NMJ exhibits a dramatic expansion in size concomitant with the expansion in volume of the muscle. Additional funding came from the Pomona College Summer Undergraduate Research Program. Recipients of these funds were MUN, JK, JC and VGG (http://www.pomona.edu/research)
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