Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Tuesday Speaker Abstracts

HIGH-AFFINITY CALCIUM SENSORS MEDIATE ASYNCHRONOUS VESICLE FUSION Skyler L. Jackman 1 ; 1 Oregon Health & Science University, Vollum Institute, Portland, OR, USA Activity-induced Ca 2+ influx typically promotes two kinetically-distinct forms of neurotransmitter release from neuronal synapses; fast synchronous vesicle fusion, followed by a slower component of asynchronous release which lasts for tens to hundreds of milliseconds. Asynchronous release is prominent in some synapse types, and is hypothesized to prolong the time window when postsynaptic cells fire. Compared to synchronous fusion, the mechanisms for asynchronous release are less well known. The high-affinity Ca 2+ -sensor synaptotagmin-7 (SYT7) was recently shown to mediate a substantial component of asynchronous release. The source of the asynchronous release in the absence of SYT7 is unknown. Here we test whether asynchronous release is driven by SYT3, another high-affinity synaptotagmin which, like SYT7, localizes to presynaptic plasma membranes and promotes short-term plasticity. We recorded synaptic responses from mice lacking one or both isoforms. We find that SYT3 and SYT7 mediate two kinetically-distinct components of asynchronous release, and asynchronous release is nearly eliminated in in SYT3/7 double knockout synapses. Asynchronous release is frequently studied by substituting extracellular Ca 2+ with Sr 2+ , which increases the magnitude and time course of asynchronous release. Remarkably, Sr 2+ fails to promote asynchronous release when synapses lack both SYT3 and SYT7. Taken together, these findings suggest that SYT3 and SYT7 are the primary drivers of asynchronous release, and the relative expression levels of each isoform may allow synapses to tailor the properties of asynchronous release.

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