Faculty Opinions recommendation of Chemical synapses without synaptic vesicles: Purinergic neurotransmission through a CALHM1 channel-mitochondrial signaling complex.

At chemical synapses, neurotransmitters are packaged into synaptic vesicles that release their contents in response to depolarization. Despite its central role in synaptic function, regulation of the machinery that loads vesicles with neurotransmitters remains poorly understood. We find that synaptic glutamate signaling in a C. elegans chemosensory circuit is regulated by antagonistic interactions between the canonical vesicular glutamate transporter EAT-4/VGLUT and another vesicular transporter, VST-1. Loss of VST-1 strongly potentiates glutamate release from chemosensory BAG neurons and disrupts chemotaxis behavior. Analysis of the circuitry downstream of BAG neurons shows that excess glutamate release disrupts behavior by inappropriately recruiting RIA interneurons to the BAG-associated chemotaxis circuit. Our data indicate that in vivo the strength of glutamatergic synapses is controlled by regulation of neurotransmitter packaging into synaptic vesicles via functional coupling of VGLUT and VST-1.

Download Full-text

Opponent vesicular transporters regulate the strength of glutamatergic neurotransmission in a C. elegans sensory circuit

Nature Communications ◽

10.1038/s41467-021-26575-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jung-Hwan Choi ◽

Lauren Bayer Horowitz ◽

Niels Ringstad

Keyword(s):

Synaptic Vesicles ◽

Glutamate Release ◽

Glutamate Transporter ◽

Synaptic Function ◽

Functional Coupling ◽

Glutamate Signaling ◽

C Elegans ◽

Vesicular Transporters ◽

Chemical Synapses

AbstractAt chemical synapses, neurotransmitters are packaged into synaptic vesicles that release their contents in response to depolarization. Despite its central role in synaptic function, regulation of the machinery that loads vesicles with neurotransmitters remains poorly understood. We find that synaptic glutamate signaling in a C. elegans chemosensory circuit is regulated by antagonistic interactions between the canonical vesicular glutamate transporter EAT-4/VGLUT and another vesicular transporter, VST-1. Loss of VST-1 strongly potentiates glutamate release from chemosensory BAG neurons and disrupts chemotaxis behavior. Analysis of the circuitry downstream of BAG neurons shows that excess glutamate release disrupts behavior by inappropriately recruiting RIA interneurons to the BAG-associated chemotaxis circuit. Our data indicate that in vivo the strength of glutamatergic synapses is controlled by regulation of neurotransmitter packaging into synaptic vesicles via functional coupling of VGLUT and VST-1.

Download Full-text

Active zone assembly and synaptic release

Biochemical Society Transactions ◽

10.1042/bst0340939 ◽

2006 ◽

Vol 34 (5) ◽

pp. 939-941 ◽

Cited By ~ 18

Author(s):

R.J. Kittel ◽

S. Hallermann ◽

S. Thomsen ◽

C. Wichmann ◽

S.J. Sigrist ◽

...

Keyword(s):

Calcium Channels ◽

Active Zone ◽

Synaptic Vesicles ◽

Spatial Arrangement ◽

Transmission Characteristics ◽

Vesicle Release ◽

Synaptic Release ◽

Voltage Gated Calcium Channels ◽

Presynaptic Calcium ◽

Chemical Synapses

Neurotransmitter release at chemical synapses occurs when synaptic vesicles fuse to the presynaptic membrane at a specialized site termed the active zone. The depolarization-induced fusion is highly dependent on calcium ions, and, correspondingly, the transmission characteristics of synapses are thought to be influenced by the spatial arrangement of voltage-gated calcium channels with respect to vesicle release sites. Here, we review the involvement of the Drosophila Bruchpilot (BRP) protein in active zone assembly, a process that is required for the clustering of presynaptic calcium channels to ensure efficient vesicle release.

Download Full-text

Optical Mesurements of Presynaptic Function: What Keeps Vesicle Traffic Going

Microscopy and Microanalysis ◽

10.1017/s1431927600025228 ◽

1998 ◽

Vol 4 (S2) ◽

pp. 1020-1021

Author(s):

Timothy A. Ryan

Keyword(s):

Nervous System ◽

Synaptic Vesicles ◽

Hippocampal Neurons ◽

Brain Cells ◽

Membrane Recycling ◽

Large Collection ◽

Vesicle Traffic ◽

Presynaptic Function ◽

Average Total Number ◽

Chemical Synapses

The nervous system has evolved to make use of a variety of mechanisms that allow information to flow and be processed among a large collection of individual cells. The communication between individual brain cells occurs largely at chemical synapses. In these compartments, chemical messengers are packaged into small vesicles that fuse with the cell membrane upon stimulation, releasing neurotransmitter.. The average total number of synaptic vesicles in a typical central nervous system synapse is only a few hundred and as a result an efficient local recycling mechanism operates in order to replenish this pool during periods of even modest neuronal activity. Without this membrane recycling, synapses quickly become depleted of vesicles, and soon fail to communicate information between cells.We make use of optical techniques to follow the trafficking of synaptic vesicles at synapses formed between hippocampal neurons grown in culture. Recycling synaptic vesicles can be readily labeled using the fluorescent amphipathic membrane dye FM 1-43.

Download Full-text

Presynaptic Calcium Channels

International Journal of Molecular Sciences ◽

10.3390/ijms20092217 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2217 ◽

Cited By ~ 6

Author(s):

Sumiko Mochida

Keyword(s):

Neurotransmitter Release ◽

Synaptic Vesicles ◽

Neuronal Firing ◽

Regulatory Proteins ◽

Channel Modulation ◽

Signaling Complex ◽

Presynaptic Plasticity ◽

Presynaptic Calcium ◽

Ca2 Channels ◽

Α1 Subunit

Presynaptic Ca2+ entry occurs through voltage-gated Ca2+ (CaV) channels which are activated by membrane depolarization. Depolarization accompanies neuronal firing and elevation of Ca2+ triggers neurotransmitter release from synaptic vesicles. For synchronization of efficient neurotransmitter release, synaptic vesicles are targeted by presynaptic Ca2+ channels forming a large signaling complex in the active zone. The presynaptic CaV2 channel gene family (comprising CaV2.1, CaV2.2, and CaV2.3 isoforms) encode the pore-forming α1 subunit. The cytoplasmic regions are responsible for channel modulation by interacting with regulatory proteins. This article overviews modulation of the activity of CaV2.1 and CaV2.2 channels in the control of synaptic strength and presynaptic plasticity.

Download Full-text

Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms21217848 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7848 ◽

Cited By ~ 1

Author(s):

Kaspar Gierke ◽

Julia von Wittgenstein ◽

Maike Hemmerlein ◽

Jenny Atorf ◽

Anneka Joachimsthaler ◽

...

Keyword(s):

Synaptic Vesicles ◽

Bipolar Cells ◽

Visual Signal ◽

Cell Type ◽

Future Studies ◽

Mammalian Retina ◽

Chemical Synapses ◽

Important Basis ◽

The Brain

Munc13 isoforms are constituents of the presynaptic compartment of chemical synapses, where they govern important steps in preparing synaptic vesicles for exocytosis. The role of Munc13-1, -2 and -3 is well documented in brain neurons, but less is known about their function and distribution among the neurons of the retina and their conventional and ribbon-type chemical synapses. Here, we examined the retinae of Munc13-1-, -2-, and -3-EXFP knock-in (KI) mice with a combination of immunocytochemistry, physiology, and electron microscopy. We show that knock-in of Munc13-EXFP fusion proteins did not affect overall retinal anatomy or synapse structure, but slightly affected synaptic transmission. By labeling Munc13-EXFP KI retinae with specific antibodies against Munc13-1, -2 and -3, we found that unlike in the brain, most retinal synapses seem to operate with a single Munc13 isoform. A surprising exception to this rule was type 6 ON bipolar cells, which expressed two Munc13 isoforms in their synaptic terminals, ubMunc13-2 and Munc13-3. The results of this study provide an important basis for future studies on the contribution of Munc13 isoforms in visual signal processing in the mammalian retina.

Download Full-text

Is there a mitochondrial signaling complex facilitating cholesterol import?

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2006.12.004 ◽

2007 ◽

Vol 265-266 ◽

pp. 59-64 ◽

Cited By ~ 75

Author(s):

Vassilios Papadopoulos ◽

Jun Liu ◽

Martine Culty

Keyword(s):

Signaling Complex ◽

Mitochondrial Signaling

Download Full-text

Restoring synaptic vesicles during compensatory endocytosis

Essays in Biochemistry ◽

10.1042/bse0570121 ◽

2015 ◽

Vol 57 ◽

pp. 121-134 ◽

Cited By ~ 5

Author(s):

Anne Gauthier-Kemper ◽

Martin Kahms ◽

Jürgen Klingauf

Keyword(s):

Self Assembly ◽

Synaptic Vesicles ◽

Molecular Level ◽

Synaptic Cleft ◽

Electrical Signal ◽

Presynaptic Site ◽

Postsynaptic Site ◽

Protein Complement ◽

Chemical Synapses ◽

Activate Receptor

In the CNS (central nervous system), nerve cells communicate by transmitting signals from one to the next across chemical synapses. Electrical signals trigger controlled secretion of neurotransmitter by exocytosis of SV (synaptic vesicles) at the presynaptic site. Neurotransmitters diffuse across the synaptic cleft, activate receptor channels in the receiving neuron at the postsynaptic site, and thereby elicit a new electrical signal. Repetitive stimulation should result in fast depletion of fusion-competent SVs, given their limited number in the presynaptic bouton. Therefore, to support repeated rounds of release, a fast trafficking cycle is required that couples exocytosis and compensatory endocytosis. During this exo-endocytic cycle, a defined stoichiometry of SV proteins has to be preserved, that is, membrane proteins have to be sorted precisely. However, how this sorting is accomplished on a molecular level is poorly understood. In the present chapter we review recent findings regarding the molecular composition of SVs and the mechanisms that sort SV proteins during compensatory endocytosis. We identify self-assembly of SV components and individual cargo recognition by sorting adaptors as major mechanisms for maintenance of the SV protein complement.

Download Full-text

Computational modeling predicts acidic microdomains in the glutamatergic synaptic cleft

10.1101/2021.06.30.450624 ◽

2021 ◽

Author(s):

Touhid Feghhi ◽

Roberto X Hernandez ◽

Michal Stawarski ◽

Connon I Thomas ◽

Naomi Kamasawa ◽

...

Keyword(s):

Synaptic Vesicles ◽

Time Course ◽

Small Volume ◽

Reaction Diffusion ◽

Synaptic Cleft ◽

Structural Features ◽

Glutamatergic Synapses ◽

Diffusion Scheme ◽

Chemical Synapses ◽

Ph Probes

At chemical synapses, synaptic vesicles release their acidic contents into the cleft leading to the expectation that the cleft should acidify. However, fluorescent pH probes targeted to the cleft of conventional glutamatergic synapses in both fruit flies and mice reveal cleft alkalinization, rather than acidification. Here, using a reaction-diffusion scheme, we modeled pH dynamics at the Drosophila neuromuscular junction (NMJ) as glutamate, adenosine triphosphate (ATP) and protons (H+) are released into the cleft. The model incorporates bicarbonate and phosphate buffering systems as well as plasma membrane calcium-ATPase (PMCA) activity and predicts substantial cleft acidification but only for fractions of a millisecond following neurotransmitter release. Thereafter, the cleft rapidly alkalinizes and remains alkaline for over 100 milliseconds, as the PMCA removes H+ from the cleft in exchange for calcium ions (Ca2+) from adjacent pre- and post-synaptic compartments; thus recapitulating the empirical data. The extent of synaptic vesicle loading and time course of exocytosis has little influence on the magnitude of acidification. Phosphate, but not bicarbonate buffering is effective at ameliorating the magnitude and time course of the acid spike, while both buffering systems are effective at ameliorating cleft alkalinization. The small volume of the cleft levies a powerful influence on the magnitude of alkalinization and its time course. Structural features that open the cleft to adjacent spaces appear to be essential for alleviating the extent of pH disturbances accompanying neurotransmission.

Download Full-text