Figure 5.

Physiological amounts of cholesterol accelerate fusion by clustering t-SNAREs. (A) Delay times to SNARE-mediated fusion after vesicle docking versus membrane lipid composition (solid bars) and calculated number of t-SNAREs assumed recruited by diffusion to the fusion site during the delay time (striped bars). Lower amounts of cholesterol (yellow (PC/PS/PE/PIP2) and green (PC/PS/PE/PIP2/Ch)) increase delay times, consistent with the reduced lipid diffusivities, but the number of t-SNAREs recruited for fusion is unchanged. At physiological cholesterol (PC/PS/PE/PIP2/Ch+), fusion is so accelerated that there is insufficient time to recruit any additional t-SNAREs after docking, suggesting that t-SNAREs are preclustered. (B) Physiological cholesterol levels increase the probability ∼3-fold that a docked vesicle undergoes SNARE-mediated fusion (as opposed to nonspecific fusion or no fusion) before complete bleaching (∼20 s). To see this figure in color, go online.