Augmenting neurotransmitter release by enhancing the apparent Ca2+ affinity of synaptotagmin 1

作者：Rhee JS; Li LY; Shin OH; Rah JC; Rizo J; Sudhof TC; Rosenmund C^*

来源：Proceedings of the National Academy of Sciences, 2005, 102(51): 18664-18669.

DOI：10.1073/pnas.0509153102

• Ca2+ sensor
• exocytosis
• gain-of-function
• hippocampus
• synaptic transmission

Synaptotagmin 1 likely acts as a Ca2+ sensor in neurotransmitter release by Ca2+-binding to its two C2 domains. This notion was strongly supported by the observation that a mutation in the C2A domain causes parallel decreases in the apparent Ca2+ affinity of synaptotagmin 1 and in the Ca2+ sensitivity of release. However, this study was based on a single loss-of-function mutation. We now show that tryptophan substitutions in the synaptotagmin 1 C2 domains act as gain-of-function mutations to increase the apparent Ca2+ affinity of synaptotagmin 1. The same substitutions, when introduced into synaptotagmin 1 expressed in neurons, enhance the Ca2+ sensitivity of release. Mutations in the two C2 domains lead to comparable and additive effects in release. Our results thus show that the apparent Ca2+ sensitivity of release is dictated by the apparent Ca2+ affinity of synaptotagmin 1 in both directions, and that Ca2+ binding to both C2 domains contributes to Ca2+ triggering of release.

• 出版日期2005-12-20