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

Science ◽  
2005 ◽  
Vol 310 (5749) ◽  
pp. 858-863 ◽  
Author(s):  
Motojiro Yoshihara ◽  
Bill Adolfsen ◽  
Kathleen T. Galle ◽  
J. Troy Littleton
Keyword(s):  
Neuromuscular Junctions ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
High Frequency Stimulation ◽  
Synaptic Differentiation ◽  
Presynaptic Release ◽  
Dependent Protein ◽  
Frequency Stimulation ◽  
Retrograde Signal ◽  
Postsynaptic Calcium

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.

scholarly journals Dibutyryl cyclic adenosine monophosphate reduces expression of c-myc during HL-60 differentiation

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 412-416
Author(s):  
SS Jr McCachren ◽  
J Nichols ◽  
RE Kaufman ◽  
JE Niedel
Keyword(s):  
Leukemia Cell ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Mechanisms Of Action ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
Dependent Protein Kinase ◽  
Rna Transcripts ◽  
Dependent Protein ◽  
Promyelocytic Leukemia Cell Line

The human promyelocytic leukemia cell line HL-60 is induced to differentiate along a myelocytic pathway by dibutyryl cyclic adenosine monophosphate (dbcAMP). Other cAMP analogs are ineffective as inducing agents. The effect of these compounds on expression of c-myc was investigated using a DNA probe for c-myc to detect RNA transcripts. The dose response and time to commitment for reduction in c-myc expression with dbcAMP was similar to the findings for phenotypic changes. Bromo- cyclic AMP and butyrate alone caused no changes in c-myc expression in 24 hours, but demonstrated dramatic synergism together, suggesting that butyrate contributes in part to the effects of dbcAMP. Evidence for mechanisms of action of cAMP other than activation of the cAMP- dependent protein kinase is reviewed.

scholarly journals Microglia control the glycinergic but not the GABAergic synapses via prostaglandin E2 in the spinal cord

2017 ◽  
Vol 216 (9) ◽  
pp. 2979-2989 ◽  
Author(s):  
Yasmine Cantaut-Belarif ◽  
Myriam Antri ◽  
Rocco Pizzarelli ◽  
Sabrina Colasse ◽  
Ilaria Vaccari ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Brain Diseases ◽  
Excitatory Synapses ◽  
Diffusion Dynamics ◽  
Gabaergic Synapses ◽  
Dependent Protein ◽  
Activity Dependent ◽  
Early Features

Microglia control excitatory synapses, but their role in inhibitory neurotransmission has been less well characterized. Herein, we show that microglia control the strength of glycinergic but not GABAergic synapses via modulation of the diffusion dynamics and synaptic trapping of glycine (GlyR) but not GABAA receptors. We further demonstrate that microglia regulate the activity-dependent plasticity of glycinergic synapses by tuning the GlyR diffusion trap. This microglia–synapse cross talk requires production of prostaglandin E2 by microglia, leading to the activation of neuronal EP2 receptors and cyclic adenosine monophosphate–dependent protein kinase. Thus, we now provide a link between microglial activation and synaptic dysfunctions, which are common early features of many brain diseases.

scholarly journals Dibutyryl cyclic adenosine monophosphate reduces expression of c-myc during HL-60 differentiation

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 412-416 ◽  
Author(s):  
SS Jr McCachren ◽  
J Nichols ◽  
RE Kaufman ◽  
JE Niedel
Keyword(s):  
Leukemia Cell ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Mechanisms Of Action ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
Dependent Protein Kinase ◽  
Rna Transcripts ◽  
Dependent Protein ◽  
Promyelocytic Leukemia Cell Line

Abstract The human promyelocytic leukemia cell line HL-60 is induced to differentiate along a myelocytic pathway by dibutyryl cyclic adenosine monophosphate (dbcAMP). Other cAMP analogs are ineffective as inducing agents. The effect of these compounds on expression of c-myc was investigated using a DNA probe for c-myc to detect RNA transcripts. The dose response and time to commitment for reduction in c-myc expression with dbcAMP was similar to the findings for phenotypic changes. Bromo- cyclic AMP and butyrate alone caused no changes in c-myc expression in 24 hours, but demonstrated dramatic synergism together, suggesting that butyrate contributes in part to the effects of dbcAMP. Evidence for mechanisms of action of cAMP other than activation of the cAMP- dependent protein kinase is reviewed.

scholarly journals L-Type Calcium Channels Are Required for One Form of Hippocampal Mossy Fiber LTP

1998 ◽  
Vol 79 (4) ◽  
pp. 2181-2190 ◽  
Author(s):  
Ajay Kapur ◽  
Mark F. Yeckel ◽  
Richard Gray ◽  
Daniel Johnston
Keyword(s):  
Calcium Channels ◽  
High Frequency ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Calcium Influx ◽  
Calcium Transients ◽  
High Frequency Stimulation ◽  
Frequency Stimulation ◽  
Ca3 Pyramidal Neurons ◽  
Postsynaptic Calcium

Kapur, Ajay, Mark F. Yeckel, Richard Gray, and Daniel Johnston. L-type calcium channels are required for one form of hippocampal mossy fiber LTP. J. Neurophysiol. 79: 2181–2190, 1998. The requirement of postsynaptic calcium influx via L-type channels for the induction of long-term potentiation (LTP) of mossy fiber input to CA3 pyramidal neurons was tested for two different patterns of stimulation. Two types of LTP-inducing stimuli were used based on the suggestion that one of them, brief high-frequency stimulation (B-HFS), induces LTP postsynaptically, whereas the other pattern, long high-frequency stimulation (L-HFS), induces mossy fiber LTP presynaptically. To test whether or not calcium influx into CA3 pyramidal neurons is necessary for LTP induced by either pattern of stimulation, nimodipine, a L-type calcium channel antagonist, was added during stimulation. In these experiments nimodipine blocked the induction of mossy fiber LTP when B-HFS was given [34 ± 5% (mean ± SE) increase in control versus 7 ± 4% in nimodipine, P < 0.003]; in contrast, nimodipine did not block the induction of LTP with L-HFS (107 ± 10% in control vs. 80 ± 9% in nimodipine, P > 0.05). Administration of nimodipine after the induction of LTP had no effect on the expression of LTP. In addition, B- and L-HFS delivered directly to commissural/associational fibers in stratum radiatum failed to induce a N-methyl-d-aspartate-independent form of LTP, obviating the possibility that the presumed mossy fiber LTP resulted from potentiation of other synapses. Nimodipine had no effect on calcium transients recorded from mossy fiber presynaptic terminals evoked with the B-HFS paradigm but reduced postsynaptic calcium transients. Our results support the hypothesis that induction of mossy fiber LTP by B-HFS is mediated postsynaptically and requires entry of calcium through L-type channels into CA3 neurons.

scholarly journals Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Yulia Akbergenova ◽  
Karen L Cunningham ◽  
Yao V Zhang ◽  
Shirley Weiss ◽  
J Troy Littleton
Keyword(s):  
Glutamate Receptor ◽  
Neuromuscular Junctions ◽  
Field Size ◽  
High Frequency Stimulation ◽  
Receptor Subtype ◽  
Receptor Field ◽  
Synaptotagmin 1 ◽  
Synapse Maturation ◽  
Frequency Stimulation ◽  
Synaptic Vesicle Fusion

Neurons communicate through neurotransmitter release at specialized synaptic regions known as active zones (AZs). Using biosensors to visualize single synaptic vesicle fusion events at Drosophila neuromuscular junctions, we analyzed the developmental and molecular determinants of release probability (Pr) for a defined connection with ~300 AZs. Pr was heterogeneous but represented a stable feature of each AZ. Pr remained stable during high frequency stimulation and retained heterogeneity in mutants lacking the Ca2+ sensor Synaptotagmin 1. Pr correlated with both presynaptic Ca2+ channel abundance and Ca2+ influx at individual release sites. Pr heterogeneity also correlated with glutamate receptor abundance, with high Pr connections developing receptor subtype segregation. Intravital imaging throughout development revealed that AZs acquire high Pr during a multi-day maturation period, with Pr heterogeneity largely reflecting AZ age. The rate of synapse maturation was activity-dependent, as both increases and decreases in neuronal activity modulated glutamate receptor field size and segregation.

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