scholarly journals Glutamate signaling at cytoneme synapses

Science ◽  
2019 ◽  
Vol 363 (6430) ◽  
pp. 948-955 ◽  
Author(s):  
Hai Huang ◽  
Songmei Liu ◽  
Thomas B. Kornberg

We investigated the roles of components of neuronal synapses for development of the Drosophila air sac primordium (ASP). The ASP, an epithelial tube, extends specialized signaling filopodia called cytonemes that take up signals such as Dpp (Decapentaplegic, a homolog of the vertebrate bone morphogenetic protein) from the wing imaginal disc. Dpp signaling in the ASP was compromised if disc cells lacked Synaptobrevin and Synaptotagmin-1 (which function in vesicle transport at neuronal synapses), the glutamate transporter, and a voltage-gated calcium channel, or if ASP cells lacked Synaptotagmin-4 or the glutamate receptor GluRII. Transient elevations of intracellular calcium in ASP cytonemes correlate with signaling activity. Calcium transients in ASP cells depend on GluRII, are activated by l-glutamate and by stimulation of an optogenetic ion channel expressed in the wing disc, and are inhibited by EGTA and by the GluR inhibitor NASPM (1-naphthylacetyl spermine trihydrochloride). Activation of GluRII is essential but not sufficient for signaling. Cytoneme-mediated signaling is glutamatergic.

2018 ◽  
Author(s):  
Hai Huang ◽  
Songmei Liu ◽  
Thomas B. Kornberg

AbstractWe investigated the roles of neuronal synapse components for development of the Drosophila air sac primordium (ASP). The ASP, an epithelial tube, extends specialized signaling filopodia called cytonemes that take up signals such as Dpp from the wing imaginal disc. Dpp signaling in the ASP requires that disc cells express Dpp, Synaptobrevin, Synaptotagmin-1, the glutamate transporter, and a voltage-gated calcium channel, and that ASP cells express the Dpp receptor, Synaptotagmin-4 and the AMPA-type glutamate receptor GluRII. Calcium transients in ASP cytonemes correlate with signaling activity. Calcium transients in the ASP require GluRII, are activated by L-glutamate and by stimulation of an optogenetic ion channel expressed in the wing disc, and are inhibited by EGTA and NASPM. Activation of GluRII is essential but not sufficient for signaling. Cytoneme-mediated signaling is glutamatergic.SummaryParacrine signals transfer between Drosophila epithelial cells at glutamatergic synapses.


Development ◽  
1998 ◽  
Vol 125 (11) ◽  
pp. 2031-2040 ◽  
Author(s):  
M.J. Go ◽  
D.S. Eastman ◽  
S. Artavanis-Tsakonas

The Notch receptor mediates cell interactions controlling the developmental fate of a broad spectrum of undifferentiated cells. By modulating Notch signaling in specific precursor cells during Drosophila imaginal disc development, we demonstrate that Notch activity can influence cell proliferation. The activation of the Notch receptor in the wing disc induces the expression of the wing margin patterning genes vestigial and wingless, and strong mitotic activity. However, the effect of Notch signaling on cell proliferation is not the simple consequence of the upregulation of either vestigial or wingless. Vestigial and Wingless, on the contrary, display synergistic effects with Notch signaling, resulting in the stimulation of cell proliferation in imaginal discs.


2020 ◽  
Author(s):  
Ryo Hatori ◽  
Thomas B. Kornberg

AbstractMorphogen signaling proteins disperse across tissues to activate signal transduction in target cells. We investigated dispersion of Hedgehog (Hh), Wingless (Wg), and Bone morphogenic protein homolog Decapentaplegic (Dpp) in the Drosophila wing imaginal disc, and found that delivery to targets is regulated. Cells take up <5% Hh produced, and neither amounts taken up nor extent of signaling changes under conditions of Hh production from 50-200% normal amounts. Similarly, cells take up <25% Wg produced, and variation in Wg production from 50-700% normal has no effect on amounts taken up or signaling. Similar properties were observed for Dpp. Wing disc-produced Hh signals to disc-associated tracheal and myoblast as well as an approximately equal number of disc cells, but the extent of signaling in the disc is unaffected by the presence or absence of the tracheal cells and myoblasts. These findings show that target cells do not take up signaling proteins from a common pool and that both the amount and destination of delivered morphogens are regulated..SummaryThe extent of Hh, Wg, and Dpp signaling is independent of the amount of signal produced or the number of recipient cells.


2020 ◽  
Vol 45 (6) ◽  
pp. 1410-1419 ◽  
Author(s):  
Suzanne M. Underhill ◽  
Mark S. Colt ◽  
Susan G. Amara

AbstractAmphetamines and amphetamine-derivatives elevate neurotransmitter concentrations by competing with endogenous biogenic amines for reuptake. In addition, AMPHs have been shown to activate endocytosis of the dopamine transporter (DAT) which further elevates extracellular dopamine (DA). We previously found that the biochemical cascade leading to this cellular process involves entry of AMPH into the cell through the DAT, stimulation of an intracellular trace amine-associated receptor, TAAR1, and activation of the small GTPase, RhoA. We also showed that the neuronal glutamate transporter, EAAT3, undergoes endocytosis via the same cascade in DA neurons, leading to potentiation of glutamatergic inputs. Since AMPH is a transported inhibitor of both DAT and the norepinephrine transporter (NET), and EAAT3 is also expressed in norepinephrine (NE) neurons, we explored the possibility that this signaling cascade occurs in NE neurons. We found that AMPH can cause endocytosis of NET as well as EAAT3 in NE neurons. NET endocytosis is dependent on TAAR1, RhoA, intracellular calcium and CaMKII activation, similar to DAT. However, EAAT3 endocytosis is similar in all regards except its dependence upon CaMKII activation. RhoA activation is dependent on calcium, but not CaMKII, explaining a divergence in AMPH-mediated endocytosis of DAT and NET from that of EAAT3. These data indicate that AMPHs and other TAAR1 agonists can affect glutamate signaling through internalization of EAAT3 in NE as well as DA neurons.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Hai Huang ◽  
Thomas B Kornberg

The flight muscles, dorsal air sacs, wing blades, and thoracic cuticle of the Drosophila adult function in concert, and their progenitor cells develop together in the wing imaginal disc. The wing disc orchestrates dorsal air sac development by producing decapentaplegic and fibroblast growth factor that travel via specific cytonemes in order to signal to the air sac primordium (ASP). Here, we report that cytonemes also link flight muscle progenitors (myoblasts) to disc cells and to the ASP, enabling myoblasts to relay signaling between the disc and the ASP. Frizzled (Fz)-containing myoblast cytonemes take up Wingless (Wg) from the disc, and Delta (Dl)-containing myoblast cytonemes contribute to Notch activation in the ASP. Wg signaling negatively regulates Dl expression in the myoblasts. These results reveal an essential role for cytonemes in Wg and Notch signaling and for a signal relay system in the myoblasts.


2021 ◽  
Author(s):  
Jung-Hwan Choi ◽  
Lauren Bayer Horowitz ◽  
Niels Ringstad

At chemical synapses, neurotransmitters are packaged into synaptic vesicles that release their contents in response to depolarization. Despite its central role in synaptic function, regulation of the machinery that loads vesicles with neurotransmitters remains poorly understood. We find that synaptic glutamate signaling in a C. elegans chemosensory circuit is regulated by antagonistic interactions between the canonical vesicular glutamate transporter EAT-4/VGLUT and another vesicular transporter, VST-1. Loss of VST-1 strongly potentiates glutamate release from chemosensory BAG neurons and disrupts chemotaxis behavior. Analysis of the circuitry downstream of BAG neurons shows that excess glutamate release disrupts behavior by inappropriately recruiting RIA interneurons to the BAG-associated chemotaxis circuit. Our data indicate that in vivo the strength of glutamatergic synapses is controlled by regulation of neurotransmitter packaging into synaptic vesicles via functional coupling of VGLUT and VST-1.


Development ◽  
1981 ◽  
Vol 66 (1) ◽  
pp. 117-126
Author(s):  
Jane Karlsson ◽  
R. J. Smith

It is a general rule that of two complementary Drosophila imaginal disc fragments, one regenerates and the other duplicates. This paper reports an investigation of an exception to this rule. Duplicating fragments from the periphery of the wing disc which lacked presumptive notum were found to regenerate notum structures during and after duplication. The propensity for this was greatest in fragments lying close to the presumptive notum, with the exception of a fragment confined to the posterior compartment, which did not regenerate notum. Structures were added sequentially, and regeneration stopped once most of the notum was present. These results are not easily explained by the polar coordinate model, which states that regeneration cannot occur from duplicating fragments. Since compartments appear to be involved in this type of regeneration as in others, it is suggested that a new type of model is required, one which permits simultaneous regeneration and duplication, and assigns a major role to compartments.


2004 ◽  
Vol 324 (4) ◽  
pp. 1242-1248 ◽  
Author(s):  
Christoph Böhmer ◽  
Michaele Philippin ◽  
Jeyaganesh Rajamanickam ◽  
Andreas Mack ◽  
Stefan Broer ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jung-Hwan Choi ◽  
Lauren Bayer Horowitz ◽  
Niels Ringstad

AbstractAt chemical synapses, neurotransmitters are packaged into synaptic vesicles that release their contents in response to depolarization. Despite its central role in synaptic function, regulation of the machinery that loads vesicles with neurotransmitters remains poorly understood. We find that synaptic glutamate signaling in a C. elegans chemosensory circuit is regulated by antagonistic interactions between the canonical vesicular glutamate transporter EAT-4/VGLUT and another vesicular transporter, VST-1. Loss of VST-1 strongly potentiates glutamate release from chemosensory BAG neurons and disrupts chemotaxis behavior. Analysis of the circuitry downstream of BAG neurons shows that excess glutamate release disrupts behavior by inappropriately recruiting RIA interneurons to the BAG-associated chemotaxis circuit. Our data indicate that in vivo the strength of glutamatergic synapses is controlled by regulation of neurotransmitter packaging into synaptic vesicles via functional coupling of VGLUT and VST-1.


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