Transmembrane tethering of synaptotagmin to synaptic vesicles controls multiple modes of neurotransmitter release

Proceedings of the National Academy of Sciences of the United States of America
Jihye Lee, J T Littleton

Abstract

Synaptotagmin 1 (Syt1) is a synaptic vesicle integral membrane protein that regulates neurotransmitter release by activating fast synchronous fusion and suppressing slower asynchronous release. The cytoplasmic C2 domains of Syt1 interact with SNAREs and plasma membrane phospholipids in a Ca(2+)-dependent manner and can substitute for full-length Syt1 in in vitro membrane fusion assays. To determine whether synaptic vesicle tethering of Syt1 is required for normal fusion in vivo, we performed a structure-function study with tethering mutants at the Drosophila larval neuromuscular junction. Transgenic animals expressing only the cytoplasmic C2 domains or full-length Syt1 tethered to the plasma membrane failed to restore synchronous synaptic vesicle fusion, and also failed to clamp spontaneous vesicle release. In addition, transgenic animals with shorter, but not those with longer, linker regions separating the C2 domains from the transmembrane segment abolished Syt1's ability to activate synchronous vesicle fusion. Similar defects were observed when C2 domain alignment was altered to C2B-C2A from the normal C2A-C2B orientation, leaving the tether itself intact. Although cytoplasmic and plasma membrane-tethered Syt1 variants could...Continue Reading

References

Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·K C MartinB K Kaang
Oct 6, 1995·The Journal of Biological Chemistry·E R ChapmanR Jahn
Jan 17, 1995·Biochemical and Biophysical Research Communications·S OritaY Takai
Mar 25, 1993·Nature·T SöllnerJ E Rothman
Sep 7, 2000·The Journal of Cell Biology·R C DesaiE R Chapman
Mar 10, 2001·Nature·R Fernández-ChacónT C Südhof
Sep 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·T VoetsE Neher
Dec 7, 2002·Neuron·Motojiro Yoshihara, J Troy Littleton
Dec 24, 2002·The Journal of Biological Chemistry·Colin Rickman, Bazbek Davletov
Mar 27, 2004·Science·Ward C TuckerEdwin R Chapman
Jul 9, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tei-ichi Nishiki, George J Augustine
May 5, 2007·Science·Sascha MartensHarvey T McMahon
Sep 25, 2007·Nature Structural & Molecular Biology·Alexander SteinReinhard Jahn
Jul 12, 2008·Nature Structural & Molecular Biology·Josep Rizo, Christian Rosenmund
Jul 16, 2008·Nature Structural & Molecular Biology·Michael C ChickaEdwin R Chapman
May 5, 2009·Nature Neuroscience·Jun XuThomas C Südhof
Jun 12, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Huisheng LiuEdwin R Chapman
Jul 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hua WenPaul Brehm
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Motojiro YoshiharaJ Troy Littleton
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
Dec 21, 2011·The Journal of Cell Biology·Zhao WangEdwin R Chapman
Jan 4, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jihye LeeJ Troy Littleton
Aug 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Alpay B SevenJosep Rizo
Nov 1, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jan E MelomJ Troy Littleton
Mar 25, 2014·Nature Neuroscience·Huisheng LiuEdwin R Chapman
Mar 29, 2014·Cellular and Molecular Neurobiology·Shao-Ying HuaLiang Tong
Dec 17, 2014·Nature Communications·Chao-Chen LinPeter Jomo Walla

❮ Previous
Next ❯

Citations

Jul 20, 2016·ELife·Maria N ZanettiShyam S Krishnakumar
May 3, 2020·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Yunxia NiuFeng Jin
Jul 9, 2017·The Journal of General Physiology·Tejeshwar C RaoArun Anantharam
Aug 8, 2018·Frontiers in Synaptic Neuroscience·Claire Guerrier, David Holcman
Oct 9, 2015·Genetics·Kathryn P Harris, J Troy Littleton
Jun 22, 2018·Neural Regeneration Research·Wen-Juan FanJie-Xin Deng
Oct 27, 2017·Frontiers in Molecular Neuroscience·Zhenyong WuErdem Karatekin
May 25, 2018·Annual Review of Biophysics·Axel T BrungerQiangjun Zhou
Jul 14, 2018·FEBS Letters·Yongsoo Park, Je-Kyung Ryu
Feb 12, 2021·The Journal of Cell Biology·Lei LiZhitao Hu
Feb 24, 2021·Cellular and Molecular Life Sciences : CMLS·Mónica C Quiñones-Frías, J Troy Littleton
May 13, 2021·Molecular Biology of the Cell·Aayushi ManchandaColin P Johnson
Aug 24, 2021·Frontiers in Molecular Neuroscience·Chad W Sauvola, J Troy Littleton
Sep 4, 2020·Biophysical Journal·Ramesh Prasad, Huan-Xiang Zhou

❮ Previous
Next ❯

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

Proceedings of the National Academy of Sciences of the United States of America
Motojiro YoshiharaJ Troy Littleton
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Jihye LeeJ T Littleton
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Brie E PaddockN E Reist
Proceedings of the National Academy of Sciences of the United States of America
Sudipta SaraswatiJ T Littleton
© 2021 Meta ULC. All rights reserved