Retrograde signaling by Syt 4 induces presynaptic release and synapse-specific growth.
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 (Ca2+) 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 Ca2+ sensor to release retrograde signals that stimulate enhanced presynaptic function through activation of the cyclic adenosine monophosphate (cAMP)-cAMP-dependent protein kinase pathway. Postsynaptic Ca2+ influx also stimulates local synaptic differentiation and growth through Syt 4-mediated retrograde signals in a synapse-specific manner.
Yoshihara
Motojiro
M
Picower Institute for Learning and Memory, Department of Biology, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. motojiro@mit.edu
Adolfsen
Bill
B
Galle
Kathleen T
KT
Littleton
J Troy
JT
D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D025461:Feedback, Physiological; D008959:Models, Neurological; D009154:Mutation; D009469:Neuromuscular Junction / Q000502:physiology*; D009473:Neuronal Plasticity; D017729:Presynaptic Terminals / Q000502:physiology; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000502:physiology; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000502:physiology
D017470:Receptors, Glutamate; D004533:Egtazic Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium