Ring-like oligomers of Synaptotagmins and related C2 domain proteins

ZANETTI, MARIA N; BELLO, OSCAR D; WANG, JING; COLEMAN, JEFF; CAI, YIYING; SINDELAR, CHARLES V; ROTHMAN, JAMES E; KRISHNAKUMAR, SHYAM S

eLife

eLife Sciences Publications Ltd

Año: 2016 vol. 5

We recently reported that the C2AB portion of Synaptotagmin 1 (Syt1) could self-assemble into Ca(2+)-sensitive ring-like oligomers on membranes, which could potentially regulate neurotransmitter release. Here we report that analogous ring-like oligomers assemble from the C2AB domains of other Syt isoforms (Syt2, Syt7, Syt9) as well as related C2 domain containing protein, Doc2B and extended Synaptotagmins (E-Syts). Evidently, circular oligomerization is a general and conserved structural aspect of many C2 domain proteins, including Synaptotagmins. Further, using electron microscopy combined with targeted mutations, we show that under physiologically relevant conditions, both the Syt1 ring assembly and its rapid disruption by Ca(2+) involve the well-established functional surfaces on the C2B domain that are important for synaptic transmission. Our data suggests that ring formation may be triggered at an early step in synaptic vesicle docking and positions Syt1 to synchronize neurotransmitter release to Ca(2+) influx.