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Title: | Synaptotagmin 1 is required for vesicular Ca2+/H +-antiport activity |
Author: | Cordeiro, Joao Miguel Boda, Bernadett Gonçalves, Paula P. Dunant, Yves |
Keywords: | Ca2+/H+-antiport PC12 pheochromocytoma cells synaptic vesicles synaptotagmin |
Issue Date: | 2013 |
Publisher: | Wiley |
Abstract: | A low-affinity Ca(2+) /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 Ca(2+) -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 Ca(2+) /H(+) -antiport. We measured Ca(2+) /H(+) -antiport activity in vesicles and granules of pheochromocytoma PC12 cells by three methods: (i) Ca(2+) -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: Ca(2+) /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 Ca(2+) /H(+) -antiport activity. Therefore, in addition to its previously described functions, synaptotagmin-1 is involved in a rapid vesicular Ca(2+) sequestration through a Ca(2+) /H(+) antiport. |
Peer review: | yes |
URI: | http://hdl.handle.net/10773/24564 |
DOI: | 10.1111/jnc.12278 |
ISSN: | 0022-3042 |
Appears in Collections: | CESAM - Artigos DBio - Artigos |
Files in This Item:
File | Description | Size | Format | |
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Cordeiro et al. - 2013 - Synaptotagmin 1 is required for vesicular Ca2+H+-.pdf | 406.59 kB | Adobe PDF |
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