Mechanisms of Synaptic Vesicle Exo- and Endocytosis

Mochida, Sumiko

doi:10.3390/biomedicines10071593

Cited by 14 publications

(18 citation statements)

References 181 publications

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“…Accurate task-specific patterns of functional connectivity between large-scale brain circuits rest on well-organized processes of signal transmission and depend on synaptic integrity at the neuronal level [ 29 ]. In neurons, the information flow is conducted as an electrical signal along the axon, from dendrites to synapses, where a translation into a chemical message takes over [ 30 ]. An integral and functional synapsis is then required to spread the information flow over other neurons and allow efficient data processing in the whole central nervous system (CNS).…”

Section: The Close Relationship Between Brain Functional Connectivity...mentioning

confidence: 99%

Antipsychotics-Induced Changes in Synaptic Architecture and Functional Connectivity: Translational Implications for Treatment Response and Resistance

Bartolomeis¹,

Simone²,

Ciccarelli³

et al. 2022

Biomedicines

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Schizophrenia is a severe mental illness characterized by alterations in processes that regulate both synaptic plasticity and functional connectivity between brain regions. Antipsychotics are the cornerstone of schizophrenia pharmacological treatment and, beyond occupying dopamine D2 receptors, can affect multiple molecular targets, pre- and postsynaptic sites, as well as intracellular effectors. Multiple lines of evidence point to the involvement of antipsychotics in sculpting synaptic architecture and remodeling the neuronal functional unit. Furthermore, there is an increasing awareness that antipsychotics with different receptor profiles could yield different interregional patterns of co-activation. In the present systematic review, we explored the fundamental changes that occur under antipsychotics’ administration, the molecular underpinning, and the consequences in both acute and chronic paradigms. In addition, we investigated the relationship between synaptic plasticity and functional connectivity and systematized evidence on different topographical patterns of activation induced by typical and atypical antipsychotics.

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Section: The Close Relationship Between Brain Functional Connectivity...mentioning

confidence: 99%

Antipsychotics-Induced Changes in Synaptic Architecture and Functional Connectivity: Translational Implications for Treatment Response and Resistance

Bartolomeis¹,

Simone²,

Ciccarelli³

et al. 2022

Biomedicines

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“…4O ), demonstrating the role of SNT-1 in SV fusion (Liewald et al, 2008; Yu et al, 2013). We further observed a significantly delayed decrease of fluorescence after stimulation, indicating that SNT-1 is involved in SV recycling at C. elegans NMJs (Poskanzer et al, 2003; Mochida, 2022; τ Decay wild type = 7.9 s, τ Decay snt-1 = 43.5s; Fig. 4P, Q) .…”

Section: Resultsmentioning

confidence: 61%

“…We thus crossed the pHuji expressing transgene into mutants lacking the established SV recycling factors synaptojanin-1/UNC-26, endophilin-1/UNC-57 and synaptotagmin-1/SNT-1. These proteins are involved in numerous processes at different steps in SV recycling, such as membrane bending and clathrin-uncoating (Jorgensen et al, 1995; Harris et al, 2000; Schuske et al, 2003; Kittelmann et al, 2013; Watanabe et al, 2018; Yu et al, 2018; Mochida, 2022). Notably, SNT-1 is also the primary sensor of calcium for exocytosis but independent from this also regulates endocytosis, as an adapter complex 2 (AP2) binding site in the plasma membrane (Poskanzer et al, 2003; Yu et al, 2013; Mochida, 2022).…”

Section: Resultsmentioning

confidence: 99%

“…These proteins are involved in numerous processes at different steps in SV recycling, such as membrane bending and clathrin-uncoating (Jorgensen et al, 1995; Harris et al, 2000; Schuske et al, 2003; Kittelmann et al, 2013; Watanabe et al, 2018; Yu et al, 2018; Mochida, 2022). Notably, SNT-1 is also the primary sensor of calcium for exocytosis but independent from this also regulates endocytosis, as an adapter complex 2 (AP2) binding site in the plasma membrane (Poskanzer et al, 2003; Yu et al, 2013; Mochida, 2022). Both, unc-26(s1710) and unc-57(e406) knockout mutants, displayed a higher increase in pHuji fluorescence than wild type animals ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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pOpsicle: An all-optical reporter system for synaptic vesicle recycling combining pH-sensitive fluorescent proteins with optogenetic manipulation of neuronal activity

Seidenthal

Jánosi

Rosenkranz

et al. 2022

Preprint

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pH-sensitive fluorescent proteins are widely used to study synaptic vesicle (SV) fusion and recycling. When targeted to the lumen of SVs, fluorescence of these proteins is quenched by the acidic pH. Following SV fusion, they are exposed to extracellular neutral pH, resulting in a fluorescence increase. SV fusion, recycling and acidification can thus be tracked by tagging integral SV proteins with pHsensitive proteins. Neurotransmission is generally stimulated by electrophysiology, which is not feasible in small, intact animals, thus limiting the approach to cell culture regimes. Previous in vivo approaches depended on distinct (sensory) stimuli, thus limiting the addressable neuron types. To overcome these limitations, we established an all-optical approach to stimulate and visualize SV fusion and recycling. We combined distinct pH-sensitive fluorescent proteins (inserted into the SV protein synaptogyrin) and light-gated channelrhodopsins (ChRs) for optical stimulation, overcoming optical crosstalk and thus enabling an all-optical approach. We generated two different variants of the pHsensitive optogenetic reporter of vesicle recycling (pOpsicle) and tested them in cholinergic neurons of intact Caenorhabditis elegans nematodes. First, we combined the red fluorescent protein pHuji with the blue-light gated ChR2(H134R), and second, the green fluorescent pHluorin combined with the novel red-shifted ChR ChrimsonSA. In both cases, fluorescence increases were observed after optical stimulation. Increase and subsequent decline of fluorescence was affected by mutations of proteins involved in SV fusion and endocytosis. These results establish pOpsicle as a non-invasive, all-optical approach to investigate different steps of the SV cycle.

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“…The expert on the synaptic functions, Sumuko Mochida from Tokyo Medical University, illustrated the growing functions of synaptic active zone proteins, from their participation in various aspects of presynaptic plasticity to activity-dependent endocytosis [ 1 ].…”

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confidence: 99%