Molecular origins of synaptotagmin 1 activities on vesicle docking and fusion pore opening

Scientific Reports
Ying LaiYeon-Kyun Shin

Abstract

Synaptotagmin 1 (Syt1), a major Ca(2+) sensor in neuroexocytosis, utilizes SNARE- and membrane-binding to regulate vesicle fusion, a required process for neurotransmitter release at the synapse. However, the mechanism by which Syt1 orchestrates SNARE- and membrane- binding to control individual vesicle fusion steps is still unclear. In this study, we used a number of single vesicle assays that can differentiate intermediates of neuroexocytosis, to focus on Syt1 mutants that might impair Syt1-SNARE/PIP2 interaction, Ca(2+)-binding, or membrane penetration. Our results show that, although putative Syt1-SNARE/PIP2 coupling through the polybasic region of the C2B domain is critical for vesicle docking, its disruption does not affect content release. In contrast, Ca(2+)-binding and membrane-penetration mutants significantly reduce content release. Our results thus delineate multiple functions of Syt1 along the pathway of Ca(2+)-triggered exocytosis in unprecedented detail.

References

Apr 7, 1998·Cell·T WeberJ E Rothman
Sep 10, 1998·Nature Structural Biology·M A PoirierM K Bennett
Feb 29, 2000·The Journal of Biological Chemistry·R R GeronaT F Martin
Mar 10, 2001·Nature·R Fernández-ChacónT C Südhof
Jun 11, 2002·Nature Neuroscience·Ok-Ho ShinThomas C Südhof
Jul 3, 2002·Nature Reviews. Molecular Cell Biology·Edwin R Chapman
Jun 26, 2004·Annual Review of Neuroscience·Thomas C Sudhof
Apr 12, 2005·Nature Structural & Molecular Biology·Yibin XuYeon-Kyun Shin
Nov 4, 2005·Molecular Biology of the Cell·Colin RickmanBazbek Davletov
Dec 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·J-S RheeC Rosenmund
Apr 6, 2006·The Journal of Biological Chemistry·LiYi LiChristian Rosenmund
Jul 18, 2006·Nature Structural & Molecular Biology·Johanna R SchaubJames A McNew
May 5, 2007·Science·Sascha MartensHarvey T McMahon
Feb 16, 2008·Annual Review of Biochemistry·Edwin R Chapman
Jun 17, 2008·Nature Structural & Molecular Biology·Tae-Young YoonYeon-Kyun Shin
Jul 12, 2008·Nature Structural & Molecular Biology·Josep Rizo, Christian Rosenmund
Sep 19, 2008·Molecular Biology of the Cell·Kara L LynchThomas F J Martin
Jan 24, 2009·Science·Claudio G GiraudoJames E Rothman
Mar 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jiansong TongYeon-Kyun Shin
Jul 1, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Jiajie DiaoTaekjip Ha
Jul 3, 2009·Nature·Alexander SteinReinhard Jahn
Feb 23, 2010·Nature Structural & Molecular Biology·Marija VrljicAxel T Brunger
Feb 23, 2010·Nature Structural & Molecular Biology·Ucheor B ChoiKeith R Weninger
Nov 20, 2010·Journal of Molecular Biology·Alex L LaiDavid S Cafiso
Jun 7, 2011·Nature Structural & Molecular Biology·Enfu HuiEdwin R Chapman
Jun 7, 2011·Nature Structural & Molecular Biology·Geert van den BogaartReinhard Jahn
Jun 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Minjoung KyoungAxel T Brunger
Jul 26, 2011·Nature Structural & Molecular Biology·Shyam S KrishnakumarJames E Rothman
Dec 21, 2011·The Journal of Cell Biology·Zhao WangEdwin R Chapman
Mar 27, 2012·The Journal of Biological Chemistry·Geert van den BogaartReinhard Jahn

❮ Previous
Next ❯

Citations

Sep 22, 2015·Nature Structural & Molecular Biology·Yongsoo ParkReinhard Jahn
Jul 20, 2016·ELife·Maria N ZanettiShyam S Krishnakumar
Jan 23, 2016·Molecular Biology of the Cell·Chantell S EvansEdwin R Chapman
Sep 11, 2019·Nature Communications·Nicholas A CourtneyEdwin R Chapman
Oct 27, 2017·Frontiers in Molecular Neuroscience·Zhenyong WuErdem Karatekin
Jun 24, 2017·Frontiers in Molecular Neuroscience·Zhiwei YangLei Zhang
Nov 10, 2020·Journal of Chemical Theory and Computation·Marcelo CaparottaDiego Masone

❮ Previous
Next ❯

Methods Mentioned

BETA
circular dichroism
pull-down

Software Mentioned

smCamera

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Brie E PaddockNoreen E Reist
The Journal of Biological Chemistry
Xiaochu LouYeon-Kyun Shin
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Brie E PaddockNoreen E Reist
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
J T LittletonE R Chapman
© 2021 Meta ULC. All rights reserved