scholarly journals rbSec1A and B colocalize with syntaxin 1 and SNAP-25 throughout the axon, but are not in a stable complex with syntaxin.

1995 ◽  
Vol 129 (1) ◽  
pp. 105-120 ◽  
Author(s):  
E P Garcia ◽  
P S McPherson ◽  
T J Chilcote ◽  
K Takei ◽  
P De Camilli
Keyword(s):  
Snare Complex ◽  
Stable Complex ◽  
C Elegans ◽  
Neuronal Protein ◽  
Neurotransmitter Secretion ◽  
Synaptic Vesicle Exocytosis ◽  
Biochemical Studies ◽  
Vesicle Exocytosis ◽  
Alternatively Spliced ◽  
Affinity Interaction

rbSec1 is a mammalian neuronal protein homologous to the yeast SEC1 gene product which is required for exocytosis. Mutations in Sec1 homologues in the nervous systems of C. elegans and D. melanogaster lead to defective neurotransmitter secretion. Biochemical studies have shown that recombinant rbSec1 binds syntaxin 1 but not SNAP-25 or synaptobrevin/VAMP, the two proteins which together with syntaxin 1 form the synaptic SNARE complex. In this study we have examined the subcellular localization of rbSec1 and the degree of interaction between rbSec1 and syntaxin 1 in situ. rbSec1, which we show here to be represented by two alternatively spliced isoforms, rbSec1A and B, has a widespread distribution in the axon and is not restricted to the nerve terminal. This distribution parallels the localization of syntaxin 1 and SNAP-25 along the entire axonal plasmalemma. rbSec1 is found in a soluble and a membrane-associated form. Although a pool of rbSec1 is present on the plasmalemma, the majority of membrane-bound rbSec1 is not associated with syntaxin 1. We also show that rbSec1 is not part of the synaptic SNARE complex or of the syntaxin 1/SNAP-25 complex we show to be present in non-synaptic regions of the axon. Thus, in spite of biochemical studies demonstrating the high affinity interaction of rbSec1 and syntaxin 1, our results indicate that rbSec1 and syntaxin 1 are not stably associated. They also suggest that the function of rbSec1, syntaxin 1, and SNAP-25 is not restricted to synaptic vesicle exocytosis at the synapse.

scholarly journals Diverse modes of synaptic signaling, regulation, and plasticity distinguish two classes of C. elegans glutamatergic neurons

2017 ◽  
Author(s):  
Donovan Ventimiglia ◽  
Cornelia I. Bargmann
Keyword(s):  
Synaptic Vesicle ◽  
Neuronal Cell ◽  
Cell Types ◽  
Snare Complex ◽  
C Elegans ◽  
Synaptic Vesicle Exocytosis ◽  
High Calcium ◽  
Vesicle Exocytosis ◽  
Synaptic Dynamics

AbstractSynaptic vesicle release properties vary between neuronal cell types, but in most cases the molecular basis of this heterogeneity is unknown. Here, we compare in vivo synaptic properties of two neuronal classes in the C. elegans central nervous system, using VGLUT-pHluorin to monitor synaptic vesicle exocytosis and retrieval in intact animals. We show that the glutamatergic sensory neurons AWCON and ASH have distinct synaptic dynamics associated with tonic and phasic synaptic properties, respectively. Exocytosis in ASH and AWCON is differentially affected by SNARE-complex regulators that are present in both neurons: phasic ASH release is strongly dependent on UNC-13, whereas tonic AWCON release relies upon UNC-18 and on the protein kinase C homolog PKC-1. Exocytosis and retrieval each have two timescales in AWCON but one major timescale in ASH. Strong stimuli that elicit high calcium levels also increase exocytosis and retrieval rates in AWCON, generating distinct tonic and evoked synaptic modes. These results highlight the differential deployment of shared presynaptic proteins in neuronal cell type-specific functions.

scholarly journals Diverse modes of synaptic signaling, regulation, and plasticity distinguish two classes of C. elegans glutamatergic neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Donovan Ventimiglia ◽  
Cornelia I Bargmann
Keyword(s):  
Synaptic Vesicle ◽  
Neuronal Cell ◽  
Cell Types ◽  
Snare Complex ◽  
C Elegans ◽  
Synaptic Vesicle Exocytosis ◽  
High Calcium ◽  
Vesicle Exocytosis ◽  
Synaptic Dynamics

Synaptic vesicle release properties vary between neuronal cell types, but in most cases the molecular basis of this heterogeneity is unknown. Here, we compare in vivo synaptic properties of two neuronal classes in the C. elegans central nervous system, using VGLUT-pHluorin to monitor synaptic vesicle exocytosis and retrieval in intact animals. We show that the glutamatergic sensory neurons AWCON and ASH have distinct synaptic dynamics associated with tonic and phasic synaptic properties, respectively. Exocytosis in ASH and AWCON is differentially affected by SNARE-complex regulators that are present in both neurons: phasic ASH release is strongly dependent on UNC-13, whereas tonic AWCON release relies upon UNC-18 and on the protein kinase C homolog PKC-1. Strong stimuli that elicit high calcium levels increase exocytosis and retrieval rates in AWCON, generating distinct tonic and evoked synaptic modes. These results highlight the differential deployment of shared presynaptic proteins in neuronal cell type-specific functions.

scholarly journals SNARE Complex Oligomerization by Synaphin/Complexin Is Essential for Synaptic Vesicle Exocytosis

Cell ◽  
2001 ◽  
Vol 104 (3) ◽  
pp. 421-432 ◽  
Author(s):  
Hiroshi Tokumaru ◽  
Keiko Umayahara ◽  
Lorenzo L Pellegrini ◽  
Toru Ishizuka ◽  
Hideo Saisu ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Snare Complex ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis

scholarly journals Sphingosine Facilitates SNARE Complex Assembly and Activates Synaptic Vesicle Exocytosis

Neuron ◽  
2009 ◽  
Vol 62 (5) ◽  
pp. 683-694 ◽  
Author(s):  
Frédéric Darios ◽  
Catherine Wasser ◽  
Anastasia Shakirzyanova ◽  
Artur Giniatullin ◽  
Kerry Goodman ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Snare Complex ◽  
Complex Assembly ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis

scholarly journals Differential inhibition by botulinum neurotoxin A of cotransmitters released from autonomic vasodilator neurons

2001 ◽  
Vol 281 (5) ◽  
pp. H2124-H2132 ◽  
Author(s):  
Judy L. Morris ◽  
Phillip Jobling ◽  
Ian L. Gibbins
Keyword(s):  
Botulinum Neurotoxin ◽  
Snare Complex ◽  
Snare Proteins ◽  
Botulinum Neurotoxin A ◽  
Uterine Arteries ◽  
Synaptic Vesicle Exocytosis ◽  
Protein Receptor ◽  
Autonomic Neurons ◽  
Vesicle Exocytosis

The role of the soluble NSF attachment protein receptor (SNARE) protein complex in release of multiple cotransmitters from autonomic vasodilator neurons was examined in isolated segments of guinea pig uterine arteries treated with botulinum neurotoxin A (BoNTA; 50 nM). Western blotting of protein extracts from uterine arteries demonstrated partial cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25) to a NH2-terminal fragment of ∼24 kDa by BoNTA. BoNTA reduced the amplitude (by 70–80%) of isometric contractions of arteries in response to repeated electrical stimulation of sympathetic axons at 1 or 10 Hz. The amplitude of neurogenic relaxations mediated by neuronal nitric oxide (NO) was not affected by BoNTA, whereas the duration of peptide-mediated neurogenic relaxations to stimulation at 10 Hz was reduced (67% reduction in integrated responses). In contrast, presynaptic cholinergic inhibition of neurogenic relaxations was abolished by BoNTA. These results demonstrate that the SNARE complex has differential involvement in release of cotransmitters from the same autonomic neurons: NO release is not dependant on synaptic vesicle exocytosis, acetylcholine release from small vesicles is highly dependant on the SNARE complex, and neuropeptide release from large vesicles involves SNARE proteins that may interact differently with regulatory factors such as calcium.

scholarly journals Complexin-1 regulated transition in the assembly of single neuronal SNARE complex

2021 ◽  
Author(s):  
Hao Tongrui ◽  
Feng Nan ◽  
Gong Fan ◽  
Liu Jiaquan ◽  
Lu Ma ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Molecular Mechanism ◽  
Optical Tweezers ◽  
Neurotransmitter Release ◽  
Snare Complex ◽  
Snare Proteins ◽  
Synaptic Vesicle Exocytosis ◽  
Sensitive Factor ◽  
Vesicle Exocytosis ◽  
Vesicle Pool

Neurotransmitter release is mediated by the synaptic vesicle exocytosis. Important proteins in this process have been identified including the molecular machine Synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, and other regulators. Complexin (Cpx) is one of the vital regulators in this process. The functions of Cpx are proposed to maintain a proper primed vesicle pool by preventing its premature depletion, which facilitates the vesicle fusion in the presence of Ca2+. However, the molecular mechanism remains unclear. Using dual-trap optical tweezers, we detected the interaction of complexin-1 (CpxI) with SNARE. We found that the CpxI stabilizes partially folded SNARE complexes by competing with C-terminal of Vamp protein and interacting with the C-terminal of t-SNARE complex.

Role of C2 domain proteins during synaptic vesicle exocytosis

2010 ◽  
Vol 38 (1) ◽  
pp. 213-216 ◽  
Author(s):  
Sascha Martens
Keyword(s):  
Membrane Fusion ◽  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Calcium Concentration ◽  
Membrane Curvature ◽  
Snare Complex ◽  
C2 Domain ◽  
C2 Domains ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis

Neurotransmitter release is mediated by the fusion of synaptic vesicles with the presynaptic plasma membrane. Fusion is triggered by a rise in the intracellular calcium concentration and is dependent on the neuronal SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) complex. A plethora of molecules such as members of the MUNC13, MUNC18, complexin and synaptotagmin families act along with the SNARE complex to enable calcium-regulated synaptic vesicle exocytosis. The synaptotagmins are localized to synaptic vesicles by an N-terminal transmembrane domain and contain two cytoplasmic C2 domains. Members of the synaptotagmin family are thought to translate the rise in intracellular calcium concentration into synaptic vesicle fusion. The C2 domains of synaptotagmin-1 bind membranes in a calcium-dependent manner and in response induce a high degree of membrane curvature, which is required for its ability to trigger membrane fusion in vitro and in vivo. Furthermore, members of the soluble DOC2 (double-C2 domain) protein family have similar properties. Taken together, these results suggest that C2 domain proteins such as the synaptotagmins and DOC2s promote membrane fusion by the induction of membrane curvature in the vicinity of the SNARE complex. Given the widespread expression of C2 domain proteins in secretory cells, it is proposed that promotion of SNARE-dependent membrane fusion by the induction of membrane curvature is a widespread phenomenon.

scholarly journals Neurotransmitter Secretion along Growing Nerve Processes: Comparison with Synaptic Vesicle Exocytosis

1999 ◽  
Vol 144 (3) ◽  
pp. 507-518 ◽  
Author(s):  
Stanislav Zakharenko ◽  
Sunghoe Chang ◽  
Michael O'Donoghue ◽  
Sergey V. Popov
Keyword(s):  
Nerve Terminal ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
High Frequency Stimulation ◽  
Spinal Cord Neurons ◽  
Presynaptic Nerve Terminal ◽  
Neurotransmitter Secretion ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Membrane Components

In mature neurons, synaptic vesicles continuously recycle within the presynaptic nerve terminal. In developing axons which are free of contact with a postsynaptic target, constitutive membrane recycling is not localized to the nerve terminal; instead, plasma membrane components undergo cycles of exoendocytosis throughout the whole axonal surface (Matteoli et al., 1992; Kraszewski et al., 1995). Moreover, in growing Xenopus spinal cord neurons in culture, acetylcholine (ACh) is spontaneously secreted in the quantal fashion along the axonal shaft (Evers et al., 1989; Antonov et al., 1998). Here we demonstrate that in Xenopus neurons ACh secretion is mediated by vesicles which recycle locally within the axon. Similar to neurotransmitter release at the presynaptic nerve terminal, ACh secretion along the axon could be elicited by the action potential or by hypertonic solutions. We found that the parameters of neurotransmitter secretion at the nerve terminal and at the middle axon were strikingly similar. These results lead us to conclude that, as in the case of the presynaptic nerve terminal, synaptic vesicles involved in neurotransmitter release along the axon contain a complement of proteins for vesicle docking and Ca2+-dependent fusion. Taken together, our results support the idea that, in developing axons, the rudimentary machinery for quantal neurotransmitter secretion is distributed throughout the whole axonal surface. Maturation of this machinery in the process of synaptic development would improve the fidelity of synaptic transmission during high-frequency stimulation of the presynaptic cell.

scholarly journals Exploring the Two Coupled Conformational Changes That Activate the Munc18-1/Syntaxin-1 Complex

2021 ◽  
Vol 14 ◽  
Author(s):  
Jihong Gong ◽  
Xianping Wang ◽  
Chaoyang Cui ◽  
Yuyang Qin ◽  
Ziqi Jin ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Current Data ◽  
Snare Complex ◽  
Linker Region ◽  
Calcium Dependent ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
The Relationship ◽  
Snare Complex Formation

Calcium-dependent synaptic vesicle exocytosis is mediated by SNARE complex formation. The transition from the Munc18-1/syntaxin-1 complex to the SNARE complex is catalyzed by the Munc13-1 MUN domain and involves at least two conformational changes: opening of the syntaxin-1 linker region and extension of Munc18-1 domain 3a. However, the relationship and the action order of the two conformational changes remain not fully understood. Here, our data show that an open conformation in the syntaxin-1 linker region can bypass the requirement of the MUN NF sequence. In addition, an extended state of Munc18-1 domain 3a can compensate the role of the syntaxin-1 RI sequence. Altogether, the current data strongly support our previous notion that opening of the syntaxin-1 linker region by Munc13-1 is a key step to initiate SNARE complex assembly, and consequently, Munc18-1 domain 3a can extend its conformation to serve as a template for association of synaptobrevin-2 and syntaxin-1.

scholarly journals Epileptic Phenotypes Associated With SNAREs and Related Synaptic Vesicle Exocytosis Machinery

2022 ◽  
Vol 12 ◽  
Author(s):  
Elisa Cali ◽  
Clarissa Rocca ◽  
Vincenzo Salpietro ◽  
Henry Houlden
Keyword(s):  
Synaptic Vesicle ◽  
Neurodevelopmental Disorder ◽  
Febrile Seizures ◽  
Autism Spectrum ◽  
Snare Complex ◽  
Synaptic Vesicle Exocytosis ◽  
Protein Receptor ◽  
Genes Encoding ◽  
Associated Proteins ◽  
Vesicle Exocytosis

SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptor) are an heterogeneous family of proteins that, together with their key regulators, are implicated in synaptic vesicle exocytosis and synaptic transmission. SNAREs represent the core component of this protein complex. Although the specific mechanisms of the SNARE machinery is still not completely uncovered, studies in recent years have provided a clearer understanding of the interactions regulating the essential fusion machinery for neurotransmitter release. Mutations in genes encoding SNARE proteins or SNARE complex associated proteins have been associated with a variable spectrum of neurological conditions that have been recently defined as “SNAREopathies.” These include neurodevelopmental disorder, autism spectrum disorder (ASD), movement disorders, seizures and epileptiform abnormalities. The SNARE phenotypic spectrum associated with seizures ranges from simple febrile seizures and infantile spasms, to severe early-onset epileptic encephalopathies. Our study aims to review and delineate the epileptic phenotypes associated with dysregulation of synaptic vesicle exocytosis and transmission, focusing on the main proteins of the SNARE core complex (STX1B, VAMP2, SNAP25), tethering complex (STXBP1), and related downstream regulators.

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