Figure 8. Speculative model of effects of N-peptide deletions and LE_Open mutation on vesicular release.

(A) Native state of STX1A. (B) N-peptide deletion of STX1A leads to a decrease in Ca²⁺-sensitivity of vesicular release and short-term depression (STD) upon 10 Hz stimulation potentially through increased distance of Ca²⁺-channel synaptic vesicle (SV) coupling. (C) LE_Open mutation on STX1A increases fusogenicity and Ca²⁺-sensitivity of SVs and thus leads to a high degree of STD. It also leads to reduced global Ca²⁺-influx. (D) SV fusion proceeds normal when LE_Open mutation is combined with N-peptide deletion. LE_Open mutation dictates SV fusogenicity and Ca²⁺-influx by increasing the former and decreasing the latter.