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Publication - Professor Jeremy Henley

    RIM1α SUMOylation is required for fast synaptic vesicle exocytosis


    Girach, F, Craig, TJ, Henley, JM & Henley, JM, 2013, ‘RIM1α SUMOylation is required for fast synaptic vesicle exocytosis’. Cell Reports.


    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.

    Full details in the University publications repository