scholarly journals The auxiliary glutamate receptor subunit dSol-1 promotes presynaptic neurotransmitter release and homeostatic potentiation

2020 ◽  
Vol 117 (41) ◽  
pp. 25830-25839
Author(s):  
Beril Kiragasi ◽  
Pragya Goel ◽  
Sarah Perry ◽  
Yifu Han ◽  
Xiling Li ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Homeostatic Regulation ◽  
Auxiliary Subunits ◽  
Auxiliary Subunit ◽  
Glutamate Receptor Subunit ◽  
Synaptic Functions ◽  
Cub Domain ◽  
Active Zones ◽  
Domain Protein ◽  
Dependent Mechanism

Presynaptic glutamate receptors (GluRs) modulate neurotransmitter release and are physiological targets for regulation during various forms of plasticity. Although much is known about the auxiliary subunits associated with postsynaptic GluRs, far less is understood about presynaptic auxiliary GluR subunits and their functions. At theDrosophilaneuromuscular junction, a presynaptic GluR,DKaiR1D, localizes near active zones and operates as an autoreceptor to tune baseline transmission and enhance presynaptic neurotransmitter release in response to diminished postsynaptic GluR functionality, a process referred to as presynaptic homeostatic potentiation (PHP). Here, we identify an auxiliary subunit that collaborates with DKaiR1D to promote these synaptic functions. This subunit, dSol-1, is the homolog of theCaenorhabditis elegansCUB (Complement C1r/C1s, Uegf, Bmp1) domain protein Sol-1. We find thatdSol-1functions in neurons to facilitate baseline neurotransmission and to enable PHP expression, properties shared withDKaiR1D. Intriguingly, presynaptic overexpression ofdSol-1is sufficient to enhance neurotransmitter release through aDKaiR1D-dependent mechanism. Furthermore,dSol-1is necessary to rapidly increase the abundance of DKaiR1D receptors near active zones during homeostatic signaling. Together with recent work showing the CUB domain protein Neto2 is necessary for the homeostatic modulation of postsynaptic GluRs in mammals, our data demonstrate that dSol-1 is required for the homeostatic regulation of presynaptic GluRs. Thus, we propose that CUB domain proteins are fundamental homeostatic modulators of GluRs on both sides of the synapse.

scholarly journals The involvement of norepinephrine, neuropeptide Y, and nitric oxide in the cutaneous vasodilator response to local heating in humans

2008 ◽  
Vol 105 (1) ◽  
pp. 233-240 ◽  
Author(s):  
Gary J. Hodges ◽  
Wojciech A. Kosiba ◽  
Kun Zhao ◽  
John M. Johnson
Keyword(s):  
Nitric Oxide ◽  
Neuropeptide Y ◽  
Neurotransmitter Release ◽  
Local Heating ◽  
Axon Reflex ◽  
Laser Doppler Flow ◽  
Doppler Flow ◽  
Vasodilator Response ◽  
Oxide Synthase ◽  
Dependent Mechanism

Presynaptic blockade of cutaneous vasoconstrictor nerves (VCN) abolishes the axon reflex (AR) during slow local heating (SLH) and reduces the vasodilator response. In a two-part study, forearm sites were instrumented with microdialysis fibers, local heaters, and laser-Doppler flow probes. Sites were locally heated from 33 to 40°C over 70 min. In part 1, we tested whether this effect of VCN acted via nitric oxide synthase (NOS). In five subjects, treatments were as follows: 1) untreated; 2) bretylium, preventing neurotransmitter release; 3) NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS; and 4) combined bretylium + l-NAME. At treated sites, the AR was absent, and there was an attenuation of the ultimate vasodilation ( P < 0.05), which was not different among those sites ( P > 0.05). In part 2, we tested whether norepinephrine and/or neuropeptide Y is involved in the cutaneous vasodilator response to SLH. In seven subjects, treatments were as follows: 1) untreated; 2) propranolol and yohimbine to antagonize α- and β-receptors; 3) BIBP-3226 to antagonize Y1 receptors; and 4) combined propranolol + yohimbine + BIBP-3226. Treatment with propranolol + yohimbine or BIBP-3226 significantly increased the temperature at which AR occurred ( n = 4) or abolished it ( n = 3). The combination treatment consistently eliminated it. Importantly, ultimate vasodilation with SLH at the treated sites was significantly ( P < 0.05) less than at the control. These data suggest that norepinephrine and neuropeptide Y are important in the initiation of the AR and for achieving a complete vasodilator response. Since VCN and NOS blockade in combination do not have an inhibition greater than either alone, these data suggest that VCN promote heat-induced vasodilation via a nitric oxide-dependent mechanism.

Neurotransmitter Release: Priming at Presynaptic Active Zones

2008 ◽  
pp. 2834-2839
Author(s):  
Hiroshi Kawabe ◽  
Frederique Varoqueaux ◽  
Nils Brose
Keyword(s):  
Neurotransmitter Release ◽  
Active Zones

scholarly journals Separation of presynaptic Cav2 and Cav1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca2+ pump PMCA

2021 ◽  
Vol 118 (28) ◽  
pp. e2106621118
Author(s):  
Niklas Krick ◽  
Stefanie Ryglewski ◽  
Aylin Pichler ◽  
Arthur Bikbaev ◽  
Torsten Götz ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
Calcium Currents ◽  
Short Term ◽  
Triggered Release ◽  
Presynaptic Terminals ◽  
Dynamic Regulation ◽  
Short Term Plasticity ◽  
Separate Control ◽  
Active Zones

Synaptic vesicle (SV) release, recycling, and plastic changes of release probability co-occur side by side within nerve terminals and rely on local Ca2+ signals with different temporal and spatial profiles. The mechanisms that guarantee separate regulation of these vital presynaptic functions during action potential (AP)–triggered presynaptic Ca2+ entry remain unclear. Combining Drosophila genetics with electrophysiology and imaging reveals the localization of two different voltage-gated calcium channels at the presynaptic terminals of glutamatergic neuromuscular synapses (the Drosophila Cav2 homolog, Dmca1A or cacophony, and the Cav1 homolog, Dmca1D) but with spatial and functional separation. Cav2 within active zones is required for AP-triggered neurotransmitter release. By contrast, Cav1 localizes predominantly around active zones and contributes substantially to AP-evoked Ca2+ influx but has a small impact on release. Instead, L-type calcium currents through Cav1 fine-tune short-term plasticity and facilitate SV recycling. Separate control of SV exo- and endocytosis by AP-triggered presynaptic Ca2+ influx through different channels demands efficient measures to protect the neurotransmitter release machinery against Cav1-mediated Ca2+ influx. We show that the plasma membrane Ca2+ ATPase (PMCA) resides in between active zones and isolates Cav2-triggered release from Cav1-mediated dynamic regulation of recycling and short-term plasticity, two processes which Cav2 may also contribute to. As L-type Cav1 channels also localize next to PQ-type Cav2 channels within axon terminals of some central mammalian synapses, we propose that Cav2, Cav1, and PMCA act as a conserved functional triad that enables separate control of SV release and recycling rates in presynaptic terminals.

scholarly journals Postsynaptic synucleins mediate vesicular exocytosis of endocannabinoids

2021 ◽  
Author(s):  
Jun Ding ◽  
Eddy Albarran ◽  
Yue Sun ◽  
Yu Liu ◽  
Karthik Raju ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Light Chain ◽  
Tetanus Toxin ◽  
Neurotransmitter Release ◽  
Unexpected Finding ◽  
Optical Monitoring ◽  
Patch Pipette ◽  
Vesicular Exocytosis ◽  
Dependent Mechanism

Abstract Two seemingly unrelated questions have long motivated studies in neuroscience: How are endocannabinoids, among the most powerful modulators of synaptic transmission, released from neurons? What are the physiological functions of synucleins, key contributors to Parkinson’s Disease? Here, we report an unexpected convergence of these two questions: Endocannabinoids are released via vesicular exocytosis from postsynaptic neurons by a synuclein-dependent mechanism. Specifically, we find that deletion of all synucleins selectively blocks all endocannabinoid-dependent synaptic plasticity; this block is reversed by postsynaptic expression of wildtype but not of mutant α-synuclein. Loading postsynaptic neurons with endocannabinoids via patch-pipette dialysis suppressed presynaptic neurotransmitter release in wildtype but not in synuclein-deficient neurons, suggesting that the synuclein deletion blocks endocannabinoid release. Direct optical monitoring of endocannabinoid release confirmed the requirement of synucleins. Given the role of synucleins in vesicular exocytosis, the requirement for synucleins in endocannabinoid release indicates that endocannabinoids are secreted via exocytosis. Consistent with this hypothesis, postsynaptic expression of tetanus-toxin light chain, which cleaves synaptobrevin SNAREs, also blocked endocannabinoid-dependent plasticity and release. The unexpected finding that endocannabinoids are released via synuclein-dependent exocytosis assigns a function to synucleins and resolves a longstanding puzzle of how neurons release endocannabinoids to induce synaptic plasticity.

Building a synapse: genetic analysis of glutamatergic neurotransmission

2006 ◽  
Vol 34 (1) ◽  
pp. 64-67 ◽  
Author(s):  
P.J. Brockie ◽  
A.V. Maricq
Keyword(s):  
Nervous System ◽  
Genetic Analysis ◽  
Transmembrane Protein ◽  
Molecular Architecture ◽  
Glutamatergic Synapses ◽  
Auxiliary Subunit ◽  
Cub Domain ◽  
Important Challenge ◽  
Excitatory Neurotransmission ◽  
Vertebrate Central Nervous System

Ionotropic glutamate receptors (iGluRs) are a critical component of the vertebrate central nervous system and mediate the majority of rapid excitatory neurotransmission. However, iGluRs are not self-regulating molecules and require additional proteins in order to function properly. Understanding the molecular architecture of functional glutamatergic synapses is therefore an important challenge in neurobiology. To address this question, we combine the techniques of genetics, molecular biology and electrophysiology in the nematode Caenorhabditis elegans. To date, genetic analysis has identified a number of genes required to build a glutamatergic synapse, including the CUB-domain transmembrane protein, SOL-1, which is thought to act as an auxiliary subunit that directly modifies iGluR function. Identifying and characterizing new proteins, such as SOL-1, in the relatively simple nervous system of the worm can contribute to our understanding of how more complex vertebrate nervous systems function.

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