Review
Biochemistry & Molecular Biology
Monica C. Quinones-Frias, J. Troy Littleton
Summary: The SYT family of proteins play crucial roles in regulating membrane trafficking at neuronal synapses, participating in synchronous and asynchronous fusion of synaptic vesicles and preventing spontaneous release. Changes in SYT isoforms can alter the fusion of synaptic vesicles and regulate trafficking of other subcellular organelles. However, the exact mechanisms by which SYTs interact with lipids and other effectors are still under investigation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Karolina P. Stepien, Josep Rizo
Summary: The study demonstrates that decreasing the synaptobrevin-to-lipid ratio to very low levels leads to inefficient fusion, but synaptotagmin-1 strongly stimulates fusion under these conditions. Anchoring SNAP-25 on the syntaxin-1 liposomes dramatically enhances fusion efficiency. Additionally, there is a synergy between synaptotagmin-1 and membrane anchoring of SNAP-25, allowing efficient fusion between liposomes with low synaptobrevin densities and low syntaxin-1 densities.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Manindra Bera, Sathish Ramakrishnan, Jeff Coleman, Shyam S. Krishnakumar, James E. Rothman
Summary: In neurotransmitter release, Complexin regulates rapid vesicle fusion by clamping the SNARE complex, with a fusion delay likely induced by Synaptotagmin-1. The accessory-central domains of Complexin are crucial for its inhibitory function, with specific interactions with SNAREpins enhancing its effectiveness. The C-terminal domain promotes clamping by interacting with membranes to locally elevate Complexin concentration.
Article
Neurosciences
Boris Bouazza-Arostegui, Marcial Camacho, Marisa M. Brockmann, Sina Zobel, Christian Rosenmund
Summary: SYT1 triggers neurotransmitter release by interacting with anionic lipids in a calcium-dependent manner and negatively regulates spontaneous release; its relationship with other SYT isoforms is under investigation; in exocytosis, release probability is most sensitive to variation in SYT1 expression levels, while vesicle priming is least sensitive.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Holly Melland, Fabian Bumbak, Anna Kolesnik-Taylor, Elise Ng-Cordell, Abinayah John, Panayiotis Constantinou, Shelagh Joss, Martin Larsen, Christina Fagerberg, Lone Walentin Laulund, Jenny Thies, Frances Emslie, Marjolein Willemsen, Tjitske Kleefstra, Rolf Pfundt, Rebekah Barrick, Richard Chang, Lucy Loong, Majid Alfadhel, Jasper van der Smagt, Mathilde Nizon, Manju A. Kurian, Daniel J. Scott, Joshua J. Ziarek, Sarah L. Gordon, Kate Baker
Summary: The purpose of this study is to expand the genotypes and phenotypes of SYT1 gene mutations and identify the characteristics of this disorder. By analyzing the evidence, we determined the pathogenicity of these mutations and described the common clinical manifestations. In addition, we found that the clinical spectrum of this disease includes a broader range of severities. This study is of guiding significance for the diagnosis and molecular understanding of this rare neurodevelopmental disorder, and highlights the important role of the SYT1 gene in emotional regulation, motor control, and cognitive function.
GENETICS IN MEDICINE
(2022)
Article
Biology
Emma T. Watson, Michaela M. Pauers, Michael J. Seibert, Jason D. Vevea, Edwin R. Chapman
Summary: In this study, the egress of two transmembrane synaptic vesicle proteins, synaptotagmin 1 and synaptobrevin 2, from the soma of mature rat and mouse neurons was investigated using the RUSH system and HaloTag labeling approaches. The proteins were found to selectively enter axons with minimal entry into dendrites, contradicting the selective retention model. However, overexpression led to the spillover of proteins into dendrites, revealing the limited nature of the direct axonal trafficking pathway. Additionally, it was observed that synaptic vesicle constituents were first delivered to the presynaptic plasma membrane before being incorporated into vesicles.
Article
Biology
Bin Wang, Olga K. Dudko
Summary: A theory of action-potential-triggered neurotransmitter release is proposed and validated with existing data, showing a universal scaling law in synaptic transmission and the ability to extract unique kinetic and energetic parameters for each synapse. The theory also detects cooperativity among SNARE complexes and establishes connections between molecular constituents of synapses and synaptic function. Additionally, the theory reveals trade-off relations between transmission rate and fidelity, providing insights into the molecular-level properties of synapses in synaptic transmission functions.
Article
Biology
Abdelmoneim Eshra, Hartmut Schmidt, Jens Eilers, Stefan Hallermann
Summary: The basal free Ca2+ concentration critically controls action potential-evoked release, indicating a high-affinity Ca2+ sensor for vesicle priming. There is a surprisingly shallow and non-saturating relationship between release rate and intracellular Ca2+ concentration up to 50 μM. The rate of vesicle replenishment during sustained elevated intracellular Ca2+ concentration exhibited little Ca2+-dependence.
Article
Neurosciences
Michael J. Seibert, Chantell S. Evans, Kevin S. Stanley, Zhenyong Wu, Edwin R. Chapman
Summary: SYT9 is a Ca2+ sensor in neuroendocrine cells, but its function in neurons is unclear. In this study, it was found that SYT9 does not trigger rapid synaptic vesicle exocytosis in mouse cortical, hippocampal, or striatal neurons unless it is overexpressed. Loss of SYT9 in striatal neurons reduced the frequency of spontaneous neurotransmitter release events. Further investigation revealed that SYT9 is localized to dense-core vesicles containing substance P, and loss of SYT9 impaired SP release, causing the observed decrease in mini frequency. The study also showed that Ca2+ binding to the C2A domain of SYT9 triggered membrane fusion in vitro, and mutations disrupting this activity abolished SYT9's ability to regulate SP release and mini frequency. Therefore, it can be concluded that SYT9 indirectly regulates synaptic transmission in striatal neurons by controlling SP release.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Medicine, Research & Experimental
Weijie Yan, Jiahui Fan, Xia Zhang, Huimeng Song, Rongqi Wan, Wei Wang, Yanling Yin
Summary: The study investigated the impact of SNAP29 reduction on poststroke cognitive impairments using in vitro and in vivo ischemic models. It found that SNAP29 decrease was associated with synaptic dysfunction and cognitive deficits, without affecting neuronal survival. This suggests that strategies targeting SNAP29 could be effective in treating poststroke cognitive impairments.
Article
Biology
Christopher A. Norman, Shyam S. Krishnakumar, Yulia Timofeeva, Kirill E. Volynski
Summary: This study uses a computational modelling framework to quantitatively assess how the molecular architecture of the fusion clamp affects synaptic vesicle exocytosis. The results support the "release-of-inhibition" model of fast calcium-activated synaptic vesicle fusion and show that dual binding of synaptotagmin-1 and synaptotagmin-7 to the same SNARE complex enables synergistic regulation of neurotransmitter release kinetics and plasticity. The developed framework provides a powerful tool to test molecular models of calcium-triggered neurotransmitter release in silico.
COMMUNICATIONS BIOLOGY
(2023)
Article
Neurosciences
Shankar Ramachandran, Shelagh Rodgriguez, Mariana Potcoava, Simon Alford
Summary: This study investigates the number, subtypes, and locations of Ca2+ channels involved in neurotransmitter release at central synapses. By using single channel analysis and lattice light-sheet microscopy, the researchers discovered that a small pool of Ca2+ channels, comprising N-, P/Q-, and R-subtypes, are available to gate neurotransmitter release. They also found that as few as one channel may trigger neurotransmitter release. These findings provide important insights into the understanding of Ca2+ channel and synaptic dysfunction.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Adam Davison, Kaspar Gierke, Johann Helmut Brandstaetter, Norbert Babai
Summary: By studying the maturation process of synaptic ribbons in cone photoreceptors, it was found that ribbon attachment increases the density of synaptic vesicles, increases the pool size of readily releasable vesicles, and enhances the calcium sensitivity of glutamate release.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Editorial Material
Cell Biology
Ok-Ho Shin, Ege T. Kavalali
Summary: Research has identified multiple proteins containing C2 domains as Ca2+ sensors in neurotransmitter release, where they function together to sustain different forms of release. A novel Ca2+ sensor has been identified in C. elegans, complementing the role of synaptotagmin-1 in mediating slower evoked release. Earlier studies also suggest an evolutionarily conserved diversity of Ca2+ sensors mediating distinct forms of neurotransmitter release.
Article
Multidisciplinary Sciences
Xiling Li, Chun Chien, Yifu Han, Zihan Sun, Xun Chen, Dion Dickman
Summary: The study revealed that the Glutamate-gated chloride channel (GluCl alpha) in Drosophila neurons plays a critical role in presynaptic homeostatic depression (PHD), driving the process through an activity-dependent anionic conductance.
Article
Neurosciences
Zuxin Chen, Brati Das, Yukihiro Nakamura, David A. DiGregorio, Samuel M. Young
JOURNAL OF NEUROSCIENCE
(2015)
Article
Neurosciences
Monica S. Montesinos, Wei Dong, Kevin Goff, Brati Das, Debbie Guerrero-Given, Robert Schmalzigaug, Richard T. Premont, Rachel Satterfield, Naomi Kamasawa, Samuel M. Young
Article
Cell Biology
Chong Chen, Rachel Satterfield, Samuel M. Young, Peter Jonas
Article
Cell Biology
Chong Chen, Itaru Arai, Rachel Satterfield, Samuel M. Young, Peter Jonas
Article
Biology
Matthias Lubbert, R. Oliver Goral, Rachel Satterfield, Travis Putzke, Arn M. J. M. van den Maagdenberg, Naomi Kamasawa, Samuel M. Young
Article
Cell Biology
Elisa Duran, Maria Angeles Montes, Imane Jemal, Rachel Satterfield, Samuel Young, Guillermo Alvarez de Toledo
Article
Cell Biology
Wei Dong, Tamara Radulovic, R. Oliver Goral, Connon Thomas, Monica Suarez Montesinos, Debbie Guerrero-Given, Akari Hagiwara, Travis Putzke, Yamato Hida, Manabu Abe, Kenji Sakimura, Naomi Kamasawa, Toshihisa Ohtsuka, Samuel M. Young
Article
Biology
Laurie P. Sutton, Cesare Orlandi, Chenghui Song, Won Chan Oh, Brian S. Muntean, Keqiang Xie, Alice Filippini, Xiangyang Xie, Rachel Satterfield, Jazmine D. W. Yaeger, Kenneth J. Renner, Samuel M. Young, Baoji Xu, Hyungbae Kwon, Kirill A. Martemyanov
Article
Medicine, Research & Experimental
Francesca Maltecca, Elisa Baseggio, Francesco Consolato, Davide Mazza, Paola Podini, Samuel M. Young, Ilaria Drago, Ben A. Bahr, Aldamaria Puliti, Franca Codazzi, Angelo Quattrini, Giorgio Casari
JOURNAL OF CLINICAL INVESTIGATION
(2015)
Article
Neurosciences
Olga I. Ostrovskaya, Cesare Orlandi, Ana Fajardo-Serrano, Samuel M. Young, Rafael Lujan, Kirill A. Martemyanov
JOURNAL OF NEUROSCIENCE
(2018)
Article
Neurosciences
Matthias Lubbert, R. Oliver Goral, Christian Keine, Connon Thomas, Debbie Guerrero-Given, Travis Putzke, Rachel Satterlield, Naomi Kamasawa, Samuel M. Young
Article
Neurosciences
Connon Thomas, Christian Keine, Satoko Okayama, Rachel Satterfield, Morgan Musgrove, Debbie Guerrero-Given, Naomi Kamasawa, Samuel M. Young
JOURNAL OF NEUROSCIENCE
(2019)
Article
Biology
Christian Keine, Mohammed Al-Yaari, Tamara Radulovic, Connon Thomas, Paula Valino Ramos, Debbie Guerrero-Given, Mrinalini Ranjan, Holger Taschenberger, Naomi Kamasawa, Samuel M. Young
Summary: This study reveals the key regulatory role of Rac1 in synaptic transmission, mainly through modulating the dynamics of synaptic vesicle priming and potentially the release probability, affecting synaptic strength and short-term plasticity.
Editorial Material
Cell Biology
Samuel M. Young
Article
Audiology & Speech-Language Pathology
Osama Tarabichi, Tatiana Correa, Emre Kul, Stacia Phillips, Bahaa Darkazanly, Samuel M. Young Jr, Marlan R. Hansen
Summary: Viral vector gene therapy using Helper-dependent adenoviral vectors (HdAd) shows potential for treating hearing loss. HdAd vectors can express large or multiple genes in a cell-type specific manner. Two HdAd vectors, HdAd5 and a chimeric HdAd 5/35, were created and delivered into mice to evaluate their efficacy in inner ear gene therapy. Both HdAd vectors successfully transduced multiple cell types in the cochlea, suggesting their promise in treating hearing loss.