Myosin V regulates spatial localization of different forms of neurotransmitter release in central synapses

SUMMARYSynaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicluar (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites (Maschi et al, 2018). Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center towards periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition of myosin V also reduces preferential utilization of central release sites during MVR, leading to more spatially distributed and temporally uniform MVR that occurs farther away from the AZ center. Thus myosin V regulates both temporal and spatial utilization of release sites during two main forms of synchronous release.

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Myosin V Regulates Spatial Localization of Different Forms of Neurotransmitter Release in Central Synapses

Frontiers in Synaptic Neuroscience ◽

10.3389/fnsyn.2021.650334 ◽

2021 ◽

Vol 13 ◽

Author(s):

Dario Maschi ◽

Michael W. Gramlich ◽

Vitaly A. Klyachko

Keyword(s):

Molecular Motor ◽

Release Site ◽

Dependent Manner ◽

Myosin V ◽

Spatiotemporal Organization ◽

Spatial Shift ◽

Spatially Distributed ◽

Preferential Location ◽

Central Synapses ◽

Activity Dependent

Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicular (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites in an activity-dependent manner. Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center toward periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition of myosin V also reduces preferential utilization of central release sites during MVR, leading to more spatially distributed and temporally uniform MVR that occurs farther away from the AZ center. Using a modeling approach, we provide a conceptual framework that unites spatial and temporal functions of myosin V in vesicle release by controlling the gradient of release site release probability across the AZ, which in turn determines the spatiotemporal organization of both UVR and MVR. Thus myosin V regulates both temporal and spatial utilization of release sites during two main forms of synchronous release.

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Decision letter: Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses

10.7554/elife.39440.016 ◽

2018 ◽

Keyword(s):

Plasma Membrane ◽

Neurotransmitter Release ◽

Myosin V ◽

Central Synapses

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Author response: Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses

10.7554/elife.39440.017 ◽

2018 ◽

Author(s):

Dario Maschi ◽

Michael W Gramlich ◽

Vitaly A Klyachko

Keyword(s):

Plasma Membrane ◽

Neurotransmitter Release ◽

Author Response ◽

Myosin V ◽

Central Synapses

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Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses

eLife ◽

10.7554/elife.39440 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 13

Author(s):

Dario Maschi ◽

Michael W Gramlich ◽

Vitaly A Klyachko

Keyword(s):

Plasma Membrane ◽

Neurotransmitter Release ◽

Repetitive Stimulation ◽

Dependent Manner ◽

Myosin V ◽

Hippocampal Synapses ◽

Vesicle Exocytosis ◽

Central Synapses ◽

Synaptic Vesicle Fusion ◽

Single Vesicle

Synaptic vesicle fusion occurs at specialized release sites at the active zone. How refilling of release sites with new vesicles is regulated in central synapses remains poorly understood. Using nanoscale-resolution detection of individual release events in rat hippocampal synapses we found that inhibition of myosin V, the predominant vesicle-associated motor, strongly reduced refilling of the release sites during repetitive stimulation. Single-vesicle tracking revealed that recycling vesicles continuously shuttle between a plasma membrane pool and an inner pool. Vesicle retention at the membrane pool was regulated by neural activity in a myosin V dependent manner. Ultrastructural measurements of vesicle occupancy at the plasma membrane together with analyses of single-vesicle trajectories during vesicle shuttling between the pools suggest that myosin V acts as a vesicle tether at the plasma membrane, rather than a motor transporting vesicles to the release sites, or directly regulating vesicle exocytosis.

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Faculty Opinions recommendation of Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717992219.793473586 ◽

2013 ◽

Author(s):

Andreas Zimmer

Keyword(s):

Neurotransmitter Release ◽

Central Synapses

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Inhibition of Vesicular Secretion in Both Neuronal and Nonneuronal Cells by a Retargeted Endopeptidase Derivative ofClostridium botulinum Neurotoxin Type A

Infection and Immunity ◽

10.1128/iai.68.5.2587-2593.2000 ◽

2000 ◽

Vol 68 (5) ◽

pp. 2587-2593 ◽

Cited By ~ 53

Author(s):

John A. Chaddock ◽

John R. Purkiss ◽

Lorna M. Friis ◽

Janice D. Broadbridge ◽

Michael J. Duggan ◽

...

Keyword(s):

Neurotransmitter Release ◽

Botulinum Neurotoxin ◽

Type A ◽

Cell Types ◽

Snare Complex ◽

Cell Binding ◽

Vesicle Docking ◽

Botulinum Neurotoxin Type A ◽

Clostridial Neurotoxins ◽

Dose Dependent

ABSTRACT Clostridial neurotoxins potently and specifically inhibit neurotransmitter release in defined cell types by a mechanism that involves cleavage of specific components of the vesicle docking/fusion complex, the SNARE complex. A derivative of the type A neurotoxin fromClostridium botulinum (termed LHN/A) that retains catalytic activity can be prepared by proteolysis. The LHN/A, however, lacks the putative native binding domain (HC) of the neurotoxin and is thus unable to bind to neurons and effect inhibition of neurotransmitter release. Here we report the chemical conjugation of LHN/A to an alternative cell-binding ligand, wheat germ agglutinin (WGA). When applied to a variety of cell lines, including those that are ordinarily resistant to the effects of neurotoxin, WGA-LHN/A conjugate potently inhibits secretory responses in those cells. Inhibition of release is demonstrated to be ligand mediated and dose dependent and to occur via a mechanism involving endopeptidase-dependent cleavage of the natural botulinum neurotoxin type A substrate. These data confirm that the function of the HC domain of C. botulinumneurotoxin type A is limited to binding to cell surface moieties. The data also demonstrate that the endopeptidase and translocation functions of the neurotoxin are effective in a range of cell types, including those of nonneuronal origin. These observations lead to the conclusion that a clostridial endopeptidase conjugate that can be used to investigate SNARE-mediated processes in a variety of cells has been successfully generated.

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Diagenetic control of nitrogen isotope ratios in Holocene sapropels and recent sediments from the Eastern Mediterranean Sea

Biogeosciences Discussions ◽

10.5194/bgd-7-1131-2010 ◽

2010 ◽

Vol 7 (1) ◽

pp. 1131-1165 ◽

Cited By ~ 5

Author(s):

J. Möbius ◽

N. Lahajnar ◽

K.-C. Emeis

Keyword(s):

Organic Matter ◽

Primary Production ◽

Surface Sediments ◽

Eastern Mediterranean ◽

Nitrogen Isotope ◽

Organic C ◽

Deep Waters ◽

Spatially Distributed ◽

Temporal And Spatial ◽

Recent Sediments

Abstract. The enhanced accumulation of organic matter in Eastern Mediterranean sapropels and their unusually depleted δ15N values have been attributed to either enhanced nutrient availability which led to elevated primary production and carbon sequestration or to enhanced organic matter preservation under anoxic conditions. In order to evaluate these two hypothesis we have determined Ba/Al ratios, amino acid composition, N and organic C concentrations and δ15N on sinking particles, surface sediments, eight spatially distributed core records of the youngest sapropel S1 (10-6 ka) and older sapropels (S5, S6) from two locations. These data suggest that (i) temporal and spatial variations in δ15N of sedimentary N are driven by different degrees of diagenesis at different sites rather than by changes in N-sources or primary productivity and (ii) that present day TOC export production would suffice to create a sapropel like S1 under conditions of deep-water anoxia. This implies that both enhanced TOC accumulation and δ15N depletion in sapropels were due to the absence of oxygen in deep waters. Thus preservation plays a major role for the accumulation of organic-rich sediments casting doubt the need of enhanced primary production for sapropel formation.

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Sensitivity of hydrological models to temporal and spatial resolutions of rainfall data

Hydrology and Earth System Sciences ◽

10.5194/hess-23-2647-2019 ◽

2019 ◽

Vol 23 (6) ◽

pp. 2647-2663 ◽

Cited By ~ 12

Author(s):

Yingchun Huang ◽

András Bárdossy ◽

Ke Zhang

Keyword(s):

Spatial Resolution ◽

Temporal Resolution ◽

Model Performance ◽

Daily Rainfall ◽

High Temporal Resolution ◽

Dense Network ◽

Spatially Distributed ◽

Important Input ◽

Temporal And Spatial ◽

Improved Model

Abstract. Rainfall is the most important input for rainfall–runoff models. It is usually measured at specific sites on a daily or sub-daily timescale and requires interpolation for further application. This study aims to evaluate whether a higher temporal and spatial resolution of rainfall can lead to improved model performance. Four different gridded hourly and daily rainfall datasets with a spatial resolution of 1 km × 1 km for the state of Baden-Württemberg in Germany were constructed using a combination of data from a dense network of daily rainfall stations and a less dense network of sub-daily stations. Lumped and spatially distributed HBV models were used to investigate the sensitivity of model performance to the spatial resolution of rainfall. The four different rainfall datasets were used to drive both lumped and distributed HBV models to simulate daily discharges in four catchments. The main findings include that (1) a higher temporal resolution of rainfall improves the model performance if the station density is high; (2) a combination of observed high temporal resolution observations with disaggregated daily rainfall leads to further improvement in the tested models; and (3) for the present research, the increase in spatial resolution improves the performance of the model insubstantially or only marginally in most of the study catchments.

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