(
A) Single confocal slices of new-born mouse chromaffin cells stained against Syt-1 (α-Syt-1, mouse monoclonal α-Syt1 Synaptic Systems 105011), Syt-7 (α-Syt-7, rabbit polyconal α-Syt7, Synaptic Systems 105173) and GFP (α-GFP, chicken polyclonal Abcam ab13970) in WT cells, Syt-7 KO cells and Syt-7 KO cells overexpressing Syt-7 WT, a Syt-7 C2A-mutation (C2A*)(D225,227,233A), a Syt-7 C2B-mutation (C2B*) (D357,D359A), and a Syt-7 mutated in both C2A and C2B (C2AB*) (D225,227,233,357,359A). (
B) Quantification (mean ± SEM) of staining against Syt-1, Syt-7 and GFP normalized to Syt-7 WT cells. ***: p<0.001; ****: p<0.0001. In B, middle panel: one-way ANOVA with post-hoc Dunnett’s test; B, left and right panels: Kruskal-Wallis test with post-hoc Dunn’s test. Number of cells: Syt-7 WT: N = 20 cells; Syt-7 KO overexpressing Syt-7: N = 21; C2A* mutation: N = 20 cells; C2B* mutation: N = 20 cells; C2AB* mutation: N = 20 cells. (
C) Calcium uncaging experiment from a relatively high prestimulation [Ca
2+] in Syt-7 KO cells (vermilion), in Syt-7 KO cells overexpressing Syt-7 WT (black traces), a Syt-7 C2A-mutation (C2A*, pink traces, D225,227,233A), a Syt-7 C2B-mutation (C2B*, green traces D357,D359A), and a Syt-7 mutated in both C2A and C2B (C2AB*, blue traces, D225,227,233,357,359A). Panels are arranged as in
Figure 1A. (
D) Sizes (mean ± SEM) of the RRP. (
E) Sizes (mean ± SEM) of the SRP. (
F) Sustained rate (mean ± SEM) of secretion. *: p<0.05; **: p<0.01; ***: p<0.001; ****: p<0.0001. Kruskal-Wallis with post-hoc Dunn's Multiple Comparison test. Syt-7 KO: N = 50 cells; Syt-7 KO + Syt-7 WT: N = 52 cells, Syt-7 KO + Syt-7 C2A*: N = 30 cells, Syt-7 KO + Syt-7 C2B*: N = 22 cells, Syt-7 KO + Syt-7 C2AB*: 20 cells.