Annotated protein:Synaptotagmin-4 (Synaptotagmin IV) (SytIV). Gene symbol: SYT4. Taxonomy: Mus musculus (Mouse). Uniprot ID: P40749
antibody wiki:
SynGO gene info:SynGO data @ SYT4
Ontology domain:Biological Process
SynGO term:regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission (GO:0150035)
Synapse type(s):hippocampus, glutamatergic
Annotated paper:Dean C, et al. "Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release" Nat Neurosci. 2009 Jun;12(6):767-76 PMID:19448629
Figure(s):Fig.3, 5-8; Fig Suppl 2-5
Annotation description:Dean et al subcellularly localizes synaptotagmin-4 to brain-derived neurotrophic factor (BDNF)-containing vesicles in hippocampal neurons.
By in situ ELISA assay, the authors of the study show that syt-4 negatively regulates BDNF secretion (fig. 3).The authors show that BDNF vesicles undergo exocytosis in axons and dendrites and that syt-4 inhibits the process (Fig. 4 and 5). In addition, by comparison of WT and syt-4 KO animals, Dean et al show that postsynaptic release of BDNF modulate the rate of presynaptic synaptic vesicle exocytosis (retrograde trans-synaptic regulation) (Fig. 6 and 7). Furthermore, the loss of postsynaptic syt-4 increases quantal amplitude and syt-4 animals show enhanced LTP (fig. 8).
Evidence tracking, Biological System:Cultured neurons
Evidence tracking, Protein Targeting:Genetic transformation (eg; knockout, knockin, mutations)
Over-expression
Evidence tracking, Experiment Assay:Confocal
Whole-cell patch clamp
Field recordings
ELISA
Annotator(s):Momchil Ninov (ORCID:0000-0002-0808-7003)
Mahdokht Kohansalnodehi (ORCID:0000-0002-3898-5197)
Reinhard Jahn (ORCID:0000-0003-1542-3498)
Lab:Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany
Additional literature:Yoshihira et al use Drosophila as a model system and show that high frequency stimulation at NMJ can enhance presynaptic miniature release and that this process requires postsynaptic Ca2+ influx and postsynaptic vesicle recycling (utilization of shibire mutant).
The authors monitor syt-4 dynamics by using a syt-4 PHluorin expression in postsynaptic muscles. Lack of postsynaptic syt-4 abolishes presynaptic miniature release. Furthermore, syt 4-dependent increase in presynaptic release is shown to be similar to the one observed upon activation of presynaptic cAMP-dependent PKA.
Yoshihira et al show that postsynaptic (activity-dependent) modulation of presynaptic morphology and physiology is regulated by presynaptic PKA and postsynaptic syt-4. Based on these findings, a model is suggested, in which postsynaptic retrograde signal is released and regulates trans-synaptically presynaptic cAMP-dependent PKA. @ PMID:16272123
SynGO annotation ID:1184
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology