Sphingosine Facilitates SNARE Complex Assembly and Activates Synaptic Vesicle Exocytosis

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.

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

10.1101/2021.06.07.447331 ◽

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.

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Role of C2 domain proteins during synaptic vesicle exocytosis

Biochemical Society Transactions ◽

10.1042/bst0380213 ◽

2010 ◽

Vol 38 (1) ◽

pp. 213-216 ◽

Cited By ~ 21

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.

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Epileptic Phenotypes Associated With SNAREs and Related Synaptic Vesicle Exocytosis Machinery

Frontiers in Neurology ◽

10.3389/fneur.2021.806506 ◽

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

eLife ◽

10.7554/elife.31234 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 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.

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