Fig. 8: Model of successive phases in the assembly/disassembly of Synaptotagmin oligomers.

This model provides an explanation for the observed kinetics of Syt-1 oligomers, as presented in Fig. 3D. Based on experimental observations, the key assumptions are as follows: i. the oligomer exhibits a linear structure; ii. Additional Syt-1 primarily binds through the two ends of the oligomer; iii. All Syt-1 can dissociate from the oligomer at a rate independent of their location, and the oligomer reseals after a Syt-1 dissociates. I) Nucleation: At time 0, a first Syt-1 dimer assembles, initiating the nucleation of the Syt-1 oligomer. This nucleation seed can have two forms that determine the assembly rate of the subsequent Syt-1. The slower (resp. faster) assembly rate will lead to the smaller (resp. larger) oligomers; II) Continuous Growth: Following nucleation, the low number of Syt-1 molecules in the oligomer results in an assembly rate exceeding the disassembly rate. Hence, the oligomer experiences continuous growth due to the addition of new Syt-1; III) Plateau Phase: As the oligomer size increases, the disassembly rate eventually matches the assembly rate. Despite ongoing addition and dissociation of Syt-1, a steady state is reached and the oligomer size remains constant during this plateau phase; IV) Loop Formation: During the plateau phase, the two Syt-1 molecules at the end of the monomer eventually meet in their fluctuating movement and bind. This binding locks the oligomer in a loop; and, finally V) Size Reduction: Once the oligomer is locked, dissociation can still occur, but binding of new Syt-1 is restricted. Consequently, the oligomer size decreases during this phase.