Synaptotagmin has an essential function in synaptic vesicle positioning for synchronous release in addition to its role as a calcium sensor

Samuel M Young Jr; Erwin Neher

doi:10.1016/j.neuron.2009.07.028

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Synaptotagmin has an essential function in synaptic vesicle positioning for synchronous release in addition to its role as a calcium sensor

Journal article

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Synaptotagmin has an essential function in synaptic vesicle positioning for synchronous release in addition to its role as a calcium sensor

Samuel M Young Jr and Erwin Neher

Neuron (Cambridge, Mass.), Vol.63(4), pp.482-496

08/27/2009

DOI: 10.1016/j.neuron.2009.07.028

PMID: 19709630

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Abstract

A multitude of synaptic proteins interact at the active zones of nerve terminals to achieve the high temporal precision of neurotransmitter release in synchrony with action potentials. Though synaptotagmin has been recognized as the Ca2+ sensor for synchronous release, it may have additional roles of action. We address this question at the calyx of Held, a giant presynaptic terminal, that allows biophysical dissection of multiple roles of molecules in synaptic transmission. Using high-level expression recombinant adenoviruses, in conjunction with a stereotactic surgery in postnatal day 1 rats, we overcame the previous inability to molecular perturb the calyx by overexpression of a mutated synaptotagmin. We report that this mutation leaves intrinsic Ca2+ sensitivity of vesicles intact while it destabilizes the readily releasable pool of vesicles and loosens the tight coupling between Ca2+ influx and release, most likely by interfering with the correct positioning of vesicles with respect to Ca2+ channels.

Animals, Newborn

Amino Acid Sequence

Synaptic Vesicles - metabolism

Synaptic Vesicles - secretion

Rats, Wistar

Calcium - metabolism

Calcium Signaling - physiology

Cells, Cultured

Synaptotagmin II - genetics

Molecular Sequence Data

Rats

Synaptotagmin II - physiology

Animals

Calcium - physiology

Time Factors

Presynaptic Terminals - metabolism

Presynaptic Terminals - secretion

Calcium Signaling - genetics

Synaptic Vesicles - genetics

Details

Title: Subtitle: Synaptotagmin has an essential function in synaptic vesicle positioning for synchronous release in addition to its role as a calcium sensor
Creators: Samuel M Young Jr - Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Goettingen, Germany. syoung@gwdg.de
Erwin Neher
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.63(4), pp.482-496
Publisher: United States
DOI: 10.1016/j.neuron.2009.07.028
PMID: 19709630
ISSN: 0896-6273
eISSN: 1097-4199
Grant note: DOI: 10.13039/501100000780, name: European Commission, award: LSHM-CT-2005-019055; DOI: 10.13039/501100004189, name: Max-Planck-Gesellschaft; DOI: 10.13039/100005156, name: Alexander von Humboldt-Stiftung
Language: English
Date published: 08/27/2009
Academic Unit: Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
Record Identifier: 9984025356002771

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