Postsynaptic Syntaxin 4 negatively regulates the efficiency of neurotransmitter release

Abstract

Signaling from the postsynaptic compartment regulates multiple aspects of synaptic development and function. Syntaxin 4 (Syx4) is a plasma membrane t-SNARE that promotes the growth and plasticity of Drosophila neuromuscular junctions (NMJs) by regulating the localization of key synaptic proteins in the postsynaptic compartment. Here, we describe electrophysiological analyses and report that loss of Syx4 leads to enhanced neurotransmitter release, despite a decrease in the number of active zones. We describe a requirement for postsynaptic Syx4 in regulating several presynaptic parameters, including Ca²⁺ cooperativity and the abundance of the presynaptic calcium channel Cacophony (Cac) at active zones. These findings indicate Syx4 negatively regulates presynaptic neurotransmitter release through a retrograde signaling mechanism from the postsynaptic compartment.

Keywords:

• Drosophila
• neuromuscular junction
• synaptic transmission
• synaptic plasticity

Acknowledgements

We thank S. Sigrist and H. Aberle for sharing reagents. We thank the Bloomington Drosophila Stock Center (NIH P40OD018537), the Drosophila Genome Resource Center (NIH 2P40OD010949-10A1), and the Developmental Studies Hybridoma Bank for providing materials used in this study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by NSERC Discovery [Grant 250078] to BAS and NIH [grant NS040296] to JTL.