{'fraction_non_alphanumeric': 0.05422993492407809, 'fraction_numerical': 0.01373825018076645, 'mean_word_length': 6.562841530054645, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Synaptotagmin 1 is required for vesicular Ca2+/H+‐antiport activity

A low‐affinity Ca2+/H+‐antiport was described in the membrane of mammalian brain synaptic vesicles. Electrophysiological studies showed that this antiport contributes to the extreme brevity of excitation‐release coupling in rapid synapses. Synaptotagmin‐1, a vesicular protein interacting with membranes upon low‐affinity Ca2+‐binding, plays a major role in excitation‐release coupling, by synchronizing calcium entry with fast neurotransmitter release. Here, we report that synaptotagmin‐1 is necessary for expression of the vesicular Ca2+/H+‐antiport. We measured Ca2+/H+‐antiport activity in vesicles and granules of pheochromocytoma PC12 cells by three methods: (i) Ca2+‐induced dissipation of the vesicular H+‐gradient; (ii) bafilomycin‐sensitive calcium accumulation and (iii) pH‐jump‐induced calcium accumulation. The results were congruent and highly significant: Ca2+/H+‐antiport activity is detectable only in acidic organelles expressing functional synaptotagmin–1. In contrast, synaptotagmin‐1‐deficient cells – and cells where transgenically encoded synaptotagmin‐1 was acutely photo‐inactivated – were devoid of any Ca2+/H+‐antiport activity. Therefore, in addition to its previously described functions, synaptotagmin‐1 is involved in a rapid vesicular Ca2+ sequestration through a Ca2+/H+ antiport.