Projects per year
Abstract
The rapid, activity-dependent quantal presynaptic release of neurotransmitter is vital for
brain function. The complex process of vesicle priming, fusion and retrieval is very
precisely controlled and requires the spatio-temperal coordination of multiple proteinprotein
interactions. Here we show that posttranslational modification of the active zone
protein, Rab3 Interacting Molecule 1α (RIM1α) by the Small Ubiquitin-like Modifier-1
(SUMO-1) functions as a molecular switch to direct these interactions and is essential
for fast synaptic vesicle exocytosis. RIM1α SUMOylation at lysine residue K502
facilitates clustering of CaV2.1 and enhances the Ca2+ influx necessary for vesicular
release whereas non-SUMOylated RIM1α participates in the docking/priming of
synaptic vesicles and maintenance of active zone structure. These results demonstrate
that SUMOylation of RIM1α is a key determinant of rapid, synchronous
neurotransmitter release and the SUMO-mediated 'switching' of RIM1α between
binding proteins provides new insight into the mechanisms underpinning synaptic
function and dysfunction.
brain function. The complex process of vesicle priming, fusion and retrieval is very
precisely controlled and requires the spatio-temperal coordination of multiple proteinprotein
interactions. Here we show that posttranslational modification of the active zone
protein, Rab3 Interacting Molecule 1α (RIM1α) by the Small Ubiquitin-like Modifier-1
(SUMO-1) functions as a molecular switch to direct these interactions and is essential
for fast synaptic vesicle exocytosis. RIM1α SUMOylation at lysine residue K502
facilitates clustering of CaV2.1 and enhances the Ca2+ influx necessary for vesicular
release whereas non-SUMOylated RIM1α participates in the docking/priming of
synaptic vesicles and maintenance of active zone structure. These results demonstrate
that SUMOylation of RIM1α is a key determinant of rapid, synchronous
neurotransmitter release and the SUMO-mediated 'switching' of RIM1α between
binding proteins provides new insight into the mechanisms underpinning synaptic
function and dysfunction.
| Original language | English |
|---|---|
| Journal | Cell Reports |
| DOIs | |
| Publication status | Published - Nov 2013 |
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Dive into the research topics of 'RIM1α SUMOylation is required for fast synaptic vesicle exocytosis'. Together they form a unique fingerprint.Projects
- 4 Finished
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Mechanisms and consequences of presynaptic protein SUMOylation in the regulation of neurotransmitter release
Henley, J. M. (Principal Investigator)
31/12/13 → 29/04/17
Project: Research
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Molecular and functional characterisation of the neuronal specific de-ubiquitinase UCH-L1 and its role in neuronal polarity and axonal outgrowth
Henley, J. M. (Principal Investigator)
1/11/13 → 1/11/16
Project: Research
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PROTEIN INTERACTIONS AND POST TRANSATIONAL MODIFICATION IN THE TRAFFICKING OF NEURONAL KAINATE RECEPTORS
Henley, J. M. (Principal Investigator)
1/01/08 → 1/10/11
Project: Research