Retrograde Signaling by Syt 4 Induces Presynaptic Release and Synapse-Specific Growth

Abstract

The molecular pathways involved in retrograde signal transduction at synapses and the function of retrograde communication are poorly understood. Here, we demonstrate that postsynaptic calcium 2 + ion (Ca 2+ ) influx through glutamate receptors and subsequent postsynaptic vesicle fusion trigger a robust induction of presynaptic miniature release after high-frequency stimulation at Drosophila neuromuscular junctions. An isoform of the synaptotagmin family, synaptotagmin 4 (Syt 4), serves as a postsynaptic Ca 2+ sensor to release retrograde signals that stimulate enhanced presynaptic function through activation of the cyclic adenosine monophosphate (cAMP)–cAMP-dependent protein kinase pathway. Postsynaptic Ca 2+ influx also stimulates local synaptic differentiation and growth through Syt 4–mediated retrograde signals in a synapse-specific manner.