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SUMOylation of synapsin Ia maintains synaptic vesicle availability and is reduced in an autism mutation

Research output: Contribution to journalArticle

Original languageEnglish
Article number7728
Number of pages10
JournalNature Communications
Volume6
DOIs
DateAccepted/In press - 4 Jun 2015
DatePublished (current) - 15 Jul 2015

Abstract

Synapsins are key components of the presynaptic neurotransmitter release machinery. Their main role is to cluster synaptic vesicles (SVs) to each other and anchor them to the actin cytoskeleton to establish the reserve vesicle pool, and then release them in response to appropriate membrane depolarization. Here we demonstrate that SUMOylation of synapsin Ia (SynIa) at K687 is necessary for SynIa function. Replacement of endogenous SynIa with a non-SUMOylatable mutant decreases the size of the releasable vesicle pool and impairs stimulated SV exocytosis. SUMOylation enhances SynIa association with SVs to promote the efficient reclustering of SynIa following neuronal stimulation and maintain its presynaptic localization. The A548T mutation in SynIa is strongly associated with autism and epilepsy and we show that it leads to defective SynIa SUMOylation. These results identify SUMOylation as a fundamental regulator of SynIa function and reveal a novel link between reduced SUMOylation of SynIa and neurological disorders.

    Research areas

  • Biological sciences, Cell biology, Neuroscience

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Nature at http://www.nature.com/ncomms/2015/150715/ncomms8728/full/ncomms8728.html. Please refer to any applicable terms of use of the publisher.

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