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Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release

The efficiency and kinetics of neurotransmitter release are tightly regulated by calcium. Here, the authors explore how Synaptotagmin isoforms 1 and 7 work together to regulate this process, enabling nerve cells to decode presynaptic calcium signals.

Dipayan Bose
Manindra Bera
Shyam S. Krishnakumar
ResearchOpen Access30 Dec 2024
Nature Communications

Volume: 15, P: 1-11
Structural basis for the clamping and Ca²⁺ activation of SNARE-mediated fusion by synaptotagmin

The neuronal Ca²⁺-sensor Synapotagmin-1 (Syt1) interacts with SNARE proteins and lipid membranes and synchronizes neurotransmitter release in response to Ca²⁺-influx. Here the authors provide insights into the underlying molecular mechanism by determining the cryo-EM structure of the Syt1–SNARE complex on a lipid membrane at 10 Å resolution.

Kirill Grushin
Jing Wang
Shyam S. Krishnakumar
ResearchOpen Access03 Jun 2019
Nature Communications

Volume: 10, P: 1-12
A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion

Comparison of the prefusion and postfusion structures of complexin associated with SNAREs reveals a conformational switch in complexin, which is triggered by the zippering of three key Asp residues in the “switch” region of v-SNAREs into t-SNAREs. This causes complexin to move its accessory helix, thereby releasing the clamped state. This switch is triggered when the calcium sensor synaptotagmin binds calcium ions.

Shyam S Krishnakumar
Daniel T Radoff
James E Rothman
Research24 Jul 2011
Nature Structural & Molecular Biology

Volume: 18, P: 934-940
Direct determination of oligomeric organization of integral membrane proteins and lipids from intact customizable bilayer

Editor summary: A native-mass-spectrometry-based approach analyzes integral membrane protein–lipid complexes directly from near-physiological membrane conditions, providing information about protein oligomeric states, lipid identities, and membrane properties.

Aniruddha Panda
Fabian Giska
Kallol Gupta
Research27 Apr 2023
Nature Methods

Volume: 20, P: 891-897
The Effect of Hot and Cold Rolling on the Properties of Poly(oxymethylene)

Shyam Bahadur
Research01 Nov 1975
Polymer Journal

Volume: 7, P: 613-621
Complexin cross-links prefusion SNAREs into a zigzag array

Structural studies of complexin bound to a mimetic of a prefusion SNARE complex provide insight into how complexin 'clamps' SNARE complex assembly, thereby inhibiting membrane fusion. While the central helix of complexin is anchored to a SNARE complex, its accessory helix extends away and bridges to a second SNARE complex, generating a zigzag array incompatible with fusion.

Daniel Kümmel
Shyam S Krishnakumar
Karin M Reinisch
Research24 Jul 2011
Nature Structural & Molecular Biology

Volume: 18, P: 927-933
The release of inhibition model reproduces kinetics and plasticity of neurotransmitter release in central synapses

A computational modelling framework demonstrates how synaptotagmin-1 and −7 can jointly regulate the kinetics and plasticity of neurotransmitter release and provides a powerful tool to test molecular models of calcium-triggered release in silico.

Christopher A. Norman
Shyam S. Krishnakumar
Kirill E. Volynski
ResearchOpen Access27 Oct 2023
Communications Biology

Volume: 6, P: 1-13
AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders

Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca²⁺ transport and AMPAR currents.”

Vincenzo Salpietro
Christine L. Dixon
Henry Houlden
ResearchOpen Access12 Jul 2019
Nature Communications

Volume: 10, P: 1-16
Synaptotagmin-1 membrane binding is driven by the C2B domain and assisted cooperatively by the C2A domain

Clémence Gruget
Oscar Bello
Stephen H. Donaldson Jr
ResearchOpen Access22 Oct 2020
Scientific Reports

Volume: 10, P: 1-10
Nanodisc-cell fusion: control of fusion pore nucleation and lifetimes by SNARE protein transmembrane domains

Zhenyong Wu
Sarah M. Auclair
Erdem Karatekin
ResearchOpen Access06 Jun 2016
Scientific Reports

Volume: 6, P: 1-15

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