SNARE Regulatory Proteins in Synaptic Vesicle Fusion and Recycling

Sauvola, Chad W; Littleton, J. Troy

doi:10.3389/fnmol.2021.733138

Cited by 38 publications

(28 citation statements)

References 391 publications

(491 reference statements)

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“…These limitations may look like they would create difficulties in physiology by slowing down the fusion process, just as it was observed in the lipid mixing assay. Actually, they can be switched on or off by effectors and appear as assets used by cells and organelles to control and induce SNAREpin formation [ 40 ].…”

Section: Towards Snarepin Assembly: the Beginning ...mentioning

confidence: 99%

The beginning and the end of SNARE‐induced membrane fusion

et al. 2022

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Membrane fusion is not a spontaneous process. Physiologically, the formation of coiled-coil protein complexes, the SNAREpins, bridges the membrane of a vesicle and a target membrane, brings them in close contact and provides the energy necessary for their fusion. In this review, we utilize results from in vitro experiments and simple physics and chemistry models to dissect the kinetics and energetics of the fusion process from the encounter of the two membranes to the full expansion of a fusion pore. We find three main energy barriers that oppose the fusion process: SNAREpin initiation, fusion pore opening and expansion. SNAREpin initiation is inherent to the proteins and makes in vitro fusion kinetics experiments rather slow. The kinetics are physiologically accelerated by effectors. The energy barriers that precede pore opening and pore expansion can be overcome by several SNAREpin acting in concert.

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Section: Towards Snarepin Assembly: the Beginning ...mentioning

confidence: 99%

The beginning and the end of SNARE‐induced membrane fusion

et al. 2022

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“…We further assessed for functional defects in the boutons of NMJs. Synaptic vesicles loaded with neurotransmitters are brought close to the presynaptic membrane of the Drosophila NMJ by the concerted actions of presynaptic proteins, such as Bruchpilot (Brp) and another vesicular SNARE, Synaptotagmin (Syt), thus leading to the docking and fusion of these vesicles and concomitant release of glutamate (Quiñones-Frías and Littleton, 2021;Sauvola and Littleton, 2021). Brp and Syt are also essential at the Drosophila neuromuscular junctions for the clustering of calcium channels (Kittel et al, 2006;Wagh et al, 2006).…”

Section: Synapse Morphology and Health Arementioning

confidence: 99%

Glutamatergic Synapse Dysfunction in Drosophila Neuromuscular Junctions Can Be Rescued by Proteostasis Modulation

Chakravorty

Sharma

Sheeba

et al. 2022

Front. Mol. Neurosci.

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Glutamate is the major excitatory neurotransmitter in the nervous system, and the Drosophila glutamatergic neuromuscular junctions (NMJs) offer a tractable platform to understand excitatory synapse biology both in health and disease. Synaptopathies are neurodegenerative diseases that are associated with synaptic dysfunction and often display compromised proteostasis. One such rare, progressive neurodegenerative condition, Spinocerebellar Ataxia Type 3 (SCA3) or Machado-Joseph Disease (MJD), is characterized by cerebellar ataxia, Parkinsonism, and degeneration of motor neuron synapses. While the polyQ repeat mutant protein ataxin-3 is implicated in MJD, it is unclear how it leads to impaired synaptic function. In this study, we indicated that a Drosophila model of MJD recapitulates characteristics of neurodegenerative disorders marked by motor neuron dysfunction. Expression of 78 polyQ repeats of mutant ataxin-3 protein in Drosophila motor neurons resulted in behavioral defects, such as impaired locomotion in both larval and adult stages. Furthermore, defects in eclosion and lifespan were observed in adult flies. Detailed characterization of larval glutamatergic neuromuscular junctions (NMJs) revealed defects in morphological features along with compromised NMJ functioning. Autophagy, one of the key proteostasis pathways, is known to be impaired in the case of several synaptopathies. Our study reveals that overexpression of the autophagy-related protein Atg8a rescued behavioral defects. Thus, we present a model for glutamatergic synapse dysfunction that recapitulates synaptic and behavioral deficits and show that it is an amenable system for carrying out genetic and chemical biology screens to identify potential therapeutic targets for synaptopathies.

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“…Membrane fusion, a universal feature of eukaryotic protein trafficking, is mediated by SNARE-associated proteins that embed in opposing membranes to spontaneously drive membrane fusion and cargo exchange 36 . Additionally, the expressions of other membrane fusion proteins/lipoproteins were also up-regulated in the stationary phase (Fig.…”

Section: Significant Membrane Fusion Capability Of Pvc Bacteriamentioning

confidence: 99%

Cultured deep-sea PVC bacteria shed light on eukaryogenesis

Zheng¹,

Wang²,

Zhang

et al. 2021

Preprint

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Evolutionary relationship between prokaryotes and eukaryotes continues to fascinate biologists. Accumulated studies suggest a eukaryogenesis model based on the PVC (Planctomycetes-Verrucomicrobia-Chlamydiae) bacteria. However, a decisive PVC-based eukaryogenesis scenario has not yet been reported. Here, we isolated PVC bacteria, unique for dividing by budding and for possessing developed endomembrane systems, from the deep sea. In cultured PVC bacterial strains, we detected typical eukaryotic organelle-like structures including endoplasmic reticulum, Golgi apparatus, vesicles, vacuoles and actin/tubulin-based microfilaments. Strikingly, we observed a nucleolus-containing nucleus in a Verrucomicrobia strain, which divides by mitosis. Transcriptomic results further demonstrated abundant presence of genes associated with eukaryotic cellular processes including membrane fusion. We propose that the prominent capability of membrane fusion drives eukaryogenesis by enabling PVC bacteria to evolve eukaryotic cellular features.

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SNARE Regulatory Proteins in Synaptic Vesicle Fusion and Recycling

Cited by 38 publications

References 391 publications

The beginning and the end of SNARE‐induced membrane fusion

The beginning and the end of SNARE‐induced membrane fusion

Glutamatergic Synapse Dysfunction in Drosophila Neuromuscular Junctions Can Be Rescued by Proteostasis Modulation

Cultured deep-sea PVC bacteria shed light on eukaryogenesis

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