scholarly journals RIM-binding protein couples synaptic vesicle recruitment to release sites

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Astrid G. Petzoldt ◽  
Torsten W.B. Götz ◽  
Jan Heiner Driller ◽  
Janine Lützkendorf ◽  
Suneel Reddy-Alla ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Binding Protein ◽  
Domain Architecture ◽  
Release Site ◽  
Scaffold Proteins ◽  
Nanoscale Patterning ◽  
Conserved Domain ◽  
Strong Stimulation ◽  
Fibronectin Domains ◽  
Ca2 Channels

At presynaptic active zones, arrays of large conserved scaffold proteins mediate fast and temporally precise release of synaptic vesicles (SVs). SV release sites could be identified by clusters of Munc13, which allow SVs to dock in defined nanoscale relation to Ca2+ channels. We here show in Drosophila that RIM-binding protein (RIM-BP) connects release sites physically and functionally to the ELKS family Bruchpilot (BRP)-based scaffold engaged in SV recruitment. The RIM-BP N-terminal domain, while dispensable for SV release site organization, was crucial for proper nanoscale patterning of the BRP scaffold and needed for SV recruitment of SVs under strong stimulation. Structural analysis further showed that the RIM-BP fibronectin domains form a “hinge” in the protein center, while the C-terminal SH3 domain tandem binds RIM, Munc13, and Ca2+ channels release machinery collectively. RIM-BPs’ conserved domain architecture seemingly provides a relay to guide SVs from membrane far scaffolds into membrane close release sites.

scholarly journals Neurotransmitter Release Site Replenishment and Presynaptic Plasticity

2020 ◽  
Vol 22 (1) ◽  
pp. 327
Author(s):  
Sumiko Mochida
Keyword(s):  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
High Speed ◽  
Release Site ◽  
Short Term ◽  
Short Term Plasticity ◽  
Multiple Protein ◽  
Presynaptic Plasticity ◽  
Presynaptic Plasma Membrane ◽  
Ca2 Channels

An action potential (AP) triggers neurotransmitter release from synaptic vesicles (SVs) docking to a specialized release site of presynaptic plasma membrane, the active zone (AZ). The AP simultaneously controls the release site replenishment with SV for sustainable synaptic transmission in response to incoming neuronal signals. Although many studies have suggested that the replenishment time is relatively slow, recent studies exploring high speed resolution have revealed SV dynamics with milliseconds timescale after an AP. Accurate regulation is conferred by proteins sensing Ca2+ entering through voltage-gated Ca2+ channels opened by an AP. This review summarizes how millisecond Ca2+ dynamics activate multiple protein cascades for control of the release site replenishment with release-ready SVs that underlie presynaptic short-term plasticity.

scholarly journals A Complex of RIM2alpha and RIM-Binding Protein 2 Stabilizes Slow Voltage-Dependent Inactivation of Cochlear Inner Hair Cell Cav1.3 L-Type Ca2+ Channels

2018 ◽  
Vol 114 (3) ◽  
pp. 637a-638a
Author(s):  
Nadine J. Ortner ◽  
Alexandra Pinggera ◽  
Anita Siller ◽  
Nadja Hofer ◽  
Niels Brandt ◽  
...  
Keyword(s):  
Hair Cell ◽  
Binding Protein ◽  
Inner Hair Cell ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Ca2 Channels

scholarly journals Unique function words characterize genomic proteins

2018 ◽  
Vol 115 (26) ◽  
pp. 6703-6708 ◽  
Author(s):  
Andrea Scaiewicz ◽  
Michael Levitt
Keyword(s):  
Domain Architecture ◽  
Protein Sequences ◽  
Genomic Diversity ◽  
Unique Function ◽  
Function Word ◽  
Sequence Motif ◽  
Function Words ◽  
Conserved Domain ◽  
Sequence Profiles ◽  
Multiple Domain

Between 2009 and 2016 the number of protein sequences from known species increased 10-fold from 8 million to 85 million. About 80% of these sequences contain at least one region recognized by the conserved domain architecture retrieval tool (CDART) as a sequence motif. Motifs provide clues to biological function but CDART often matches the same region of a protein by two or more profiles. Such synonyms complicate estimates of functional complexity. We do full-linkage clustering of redundant profiles by finding maximum disjoint cliques: Each cluster is replaced by a single representative profile to give what we term a unique function word (UFW). From 2009 to 2016, the number of sequence profiles used by CDART increased by 80%; the number of UFWs increased more slowly by 30%, indicating that the number of UFWs may be saturating. The number of sequences matched by a single UFW (sequences with single domain architectures) increased as slowly as the number of different words, whereas the number of sequences matched by a combination of two or more UFWs in sequences with multiple domain architectures (MDAs) increased at the same rate as the total number of sequences. This combinatorial arrangement of a limited number of UFWs in MDAs accounts for the genomic diversity of protein sequences. Although eukaryotes and prokaryotes use very similar sets of “words” or UFWs (57% shared), the “sentences” (MDAs) are different (1.3% shared).

Spike-Mediated and Graded Inhibitory Synaptic Transmission Between Leech Interneurons: Evidence for Shared Release Sites

2006 ◽  
Vol 96 (1) ◽  
pp. 235-251 ◽  
Author(s):  
Andrei I. Ivanov ◽  
Ronald L. Calabrese
Keyword(s):  
Synaptic Transmission ◽  
Synaptic Vesicles ◽  
Low Voltage ◽  
Release Site ◽  
High Threshold ◽  
Channel Blockers ◽  
Ca Channel ◽  
Ca Channels ◽  
Inhibitory Synaptic Transmission ◽  
Graded Release

Inhibitory synaptic transmission between leech heart interneurons consist of two components: graded, gated by Ca2+ entering by low-threshold [low-voltage–activated (LVA)] Ca channels and spike-mediated, gated by Ca2+ entering by high-threshold [high-voltage–activated (HVA)] Ca channels. Changes in presynaptic background Ca2+ produced by Ca2+ influx through LVA channels modulate spike-mediated transmission, suggesting LVA channels have access to release sites controlled by HVA channels. Here we explore whether spike-mediated and graded transmission can use the same release sites and thus how Ca2+ influx by HVA and LVA Ca channels might interact to evoke neurotransmitter release. We recorded pre- and postsynaptic currents from voltage-clamped heart interneurons bathed in 0 mM Na+/5 mM Ca2+ saline. Using different stimulating paradigms and inorganic Ca channel blockers, we show that strong graded synaptic transmission can occlude high-threshold/spike-mediated synaptic transmission when evoked simultaneously. Suppression of LVA Ca currents diminishes graded release and concomitantly increases the ability of Ca2+ entering by HVA channels to release transmitter. Uncaging of Ca chelator corroborates that graded release occludes spike-mediated transmission. Our results indicate that both graded and spike-mediated synaptic transmission depend on the same readily releasable pool of synaptic vesicles. Thus Ca2+, entering cells through different Ca channels (LVA and HVA), acts to gate release of the same synaptic vesicles. The data argue for a closer location of HVA Ca channels to release sites than LVA Ca channels. The results are summarized in a conceptual model of a heart interneuron release site.

177 Effect of Androgens on the Expression of Ca2+-binding Protein, Regucalcin, and Ca2+-channels in MCF-7 Cells

2012 ◽  
Vol 48 ◽  
pp. S43
Author(s):  
R. Marques ◽  
C.V. Vaz ◽  
C.G. Peres ◽  
I. Gomes ◽  
C.R. Santos ◽  
...  
Keyword(s):  
Binding Protein ◽  
Ca2 Channels ◽  
Mcf 7

scholarly journals Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release

2016 ◽  
Vol 216 (1) ◽  
pp. 231-246 ◽  
Author(s):  
Joseph J. Bruckner ◽  
Hong Zhan ◽  
Scott J. Gratz ◽  
Monica Rao ◽  
Fiona Ukken ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Motor Behavior ◽  
Molecular Organization ◽  
Electrophysiological Studies ◽  
Circuit Function ◽  
Synaptic Vesicle Release ◽  
Ca2 Channels

The strength of synaptic connections varies significantly and is a key determinant of communication within neural circuits. Mechanistic insight into presynaptic factors that establish and modulate neurotransmitter release properties is crucial to understanding synapse strength, circuit function, and neural plasticity. We previously identified Drosophila Piccolo-RIM-related Fife, which regulates neurotransmission and motor behavior through an unknown mechanism. Here, we demonstrate that Fife localizes and interacts with RIM at the active zone cytomatrix to promote neurotransmitter release. Loss of Fife results in the severe disruption of active zone cytomatrix architecture and molecular organization. Through electron tomographic and electrophysiological studies, we find a decrease in the accumulation of release-ready synaptic vesicles and their release probability caused by impaired coupling to Ca2+ channels. Finally, we find that Fife is essential for the homeostatic modulation of neurotransmission. We propose that Fife organizes active zones to create synaptic vesicle release sites within nanometer distance of Ca2+ channel clusters for reliable and modifiable neurotransmitter release.

scholarly journals Endocytosis sustains release at photoreceptor ribbon synapses by restoring fusion competence

2018 ◽  
Vol 150 (4) ◽  
pp. 591-611 ◽  
Author(s):  
Xiangyi Wen ◽  
Matthew J. Van Hook ◽  
Justin J. Grassmeyer ◽  
Alex I. Wiesman ◽  
Grace M. Rich ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Release Site ◽  
Vesicle Fusion ◽  
Synaptic Ribbons ◽  
Light Responses ◽  
Site Structure ◽  
Ribbon Synapses ◽  
Site Function ◽  
Adjacent Site ◽  
Synaptic Exocytosis

Endocytosis is an essential process at sites of synaptic release. Not only are synaptic vesicles recycled by endocytosis, but the removal of proteins and lipids by endocytosis is needed to restore release site function at active zones after vesicle fusion. Synaptic exocytosis from vertebrate photoreceptors involves synaptic ribbons that serve to cluster vesicles near the presynaptic membrane. In this study, we hypothesize that this clustering increases the likelihood that exocytosis at one ribbon release site may disrupt release at an adjacent site and therefore that endocytosis may be particularly important for restoring release site competence at photoreceptor ribbon synapses. To test this, we combined optical and electrophysiological techniques in salamander rods. Pharmacological inhibition of dynamin-dependent endocytosis rapidly inhibits release from synaptic ribbons and slows recovery of ribbon-mediated release from paired pulse synaptic depression. Inhibiting endocytosis impairs the ability of second-order horizontal cells to follow rod light responses at frequencies as low as 2 Hz. Inhibition of endocytosis also increases lateral membrane mobility of individual Ca2+ channels, showing that it changes release site structure. Visualization of single synaptic vesicles by total internal reflection fluorescence microscopy reveals that inhibition of endocytosis reduces the likelihood of fusion among vesicles docked near ribbons and increases the likelihood that they will retreat from the membrane without fusion. Vesicle advance toward the membrane is also reduced, but the number of membrane-associated vesicles is not. Endocytosis therefore appears to be more important for restoring later steps in vesicle fusion than for restoring docking. Unlike conventional synapses in which endocytic restoration of release sites is evident only at high frequencies, endocytosis is needed to maintain release from rod ribbon synapses even at modest frequencies.

scholarly journals The Bruchpilot cytomatrix determines the size of the readily releasable pool of synaptic vesicles

2013 ◽  
Vol 202 (4) ◽  
pp. 667-683 ◽  
Author(s):  
Tanja Matkovic ◽  
Matthias Siebert ◽  
Elena Knoche ◽  
Harald Depner ◽  
Sara Mertel ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Circular Array ◽  
Membrane Domain ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Family Protein ◽  
Biochemical Identification ◽  
Macromolecular Architecture ◽  
Bar Formation ◽  
Ca2 Channels

Synaptic vesicles (SVs) fuse at a specialized membrane domain called the active zone (AZ), covered by a conserved cytomatrix. How exactly cytomatrix components intersect with SV release remains insufficiently understood. We showed previously that loss of the Drosophila melanogaster ELKS family protein Bruchpilot (BRP) eliminates the cytomatrix (T bar) and declusters Ca2+ channels. In this paper, we explored additional functions of the cytomatrix, starting with the biochemical identification of two BRP isoforms. Both isoforms alternated in a circular array and were important for proper T-bar formation. Basal transmission was decreased in isoform-specific mutants, which we attributed to a reduction in the size of the readily releasable pool (RRP) of SVs. We also found a corresponding reduction in the number of SVs docked close to the remaining cytomatrix. We propose that the macromolecular architecture created by the alternating pattern of the BRP isoforms determines the number of Ca2+ channel-coupled SV release slots available per AZ and thereby sets the size of the RRP.

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