Esytl is a candidate sensor protein for asynchronous neurotransmitter release: A screening for the unidentified calcium sensor in a synaptic vesicle-enriched proteome

摘要

Chemical communication between neurons relies on the fusion of neurotransmitter-filled synaptic vesicles, which results in neurotransmitter release. The fast or synchronous release is followed by a slower, asynchronous release that probably employs one or more calcium (Ca~(2+))-sensing proteins that is different from those involved in synchronous release. While synaptotagmin 1 and 2 (Syt1, Syt2) are sensors for synchronous release, predominantly in the forebrain and hindbrain, respectively, the Ca~(2+) sensor for asynchronous release remains unknown. Here, we performed a screening approach by employing quantitative mass spectrometry onto a synaptic vesicle-enriched sample fraction of two auditory hindbrain regions. We selected extended synaptotagmin 1 (Esyt1) as the only candidate amongst 26 identified synaptic proteins that fulfills several crucial requirements, namely a hindbrain-dominant expression pattern, specific Ca~(2+)- and phospholipid-binding properties and a localization in synaptic vesicles. Thus, we provide circumstantial evidence that Esytl may be the long sought-after second Ca~(2+) sensor for asynchronous release in the (auditory) hindbrain.