The synaptotagmin 1 linker may function as an electrostatic zipper that opens for docking but closes for fusion pore opening.

The Biochemical journal

PubMedID: 24001110

Lai Y, Lou X, Jho Y, Yoon TY, Shin YK. The synaptotagmin 1 linker may function as an electrostatic zipper that opens for docking but closes for fusion pore opening. Biochem J. 2013;.
Synaptotagmin 1 (Syt1), a major Ca2+ sensor for fast neurotransmitter release, contains tandem Ca2+-binding C2 domains (C2AB), a single transmembrane a-helix, and a highly charged 60-residue-long linker in between. Using the single vesicle docking and content mixing assay we found that the linker region of Syt1 is essential for its two signature functions: Ca2+-independent vesicle docking and Ca2+-dependent fusion pore opening. The linker contains the basic amino acid-rich N-terminal region and the acidic amino acid-rich C-terminal region. When the charge segregation was disrupted, fusion pore opening was slowed while docking was unchanged. Intramolecular disulfide cross-linking between N- and C-terminal regions of the linker or deletion of 40 residues from the linker reduced docking while enhancing pore opening. The EPR analysis showed Ca2+-induced line broadening reflecting a conformational change in the linker region. Thus, the results suggest that the electrostatically bipartite linker region might have some capacity to extend for docking and fold to facilitate pore opening.