Calcium-dependent switching of the specificity of phosphoinositide binding to synaptotagmin Journal Article
| Authors: | Schiavo, G.; Gu, Q. M.; Prestwich, G. D.; Söllner, T. H.; Rothman, J. E. |
| Article Title: | Calcium-dependent switching of the specificity of phosphoinositide binding to synaptotagmin |
| Abstract: | The synaptic vesicle membrane protein synaptotagmin (tagmin) is essential for fast, calcium-dependent, neurotransmitter release and is likely to be the calcium sensor for exocytosis, because of its many calcium- dependent properties. Polyphosphoinositides are needed for exocytosis, but it has not been known why. We now provide a possible connection between these observations with the finding that the C2B domain of tagmin 1 binds phosphatidylinositol-4,5-bisphosphate (PIns-4,5-P2), its isomer phosphatidylinositol-3,4-bisphosphate and phosphatidylinositol-3,4,5- trisphosphate (PIns-3,4,5-P3). Calcium ions switch the specificity of this binding from PIns-3,4,5-P3 (at calcium concentrations found in resting nerve terminals) to PIns-4,5-P2 (at concentration of calcium required for transmitter release). Inositol polyphosphates, known blockers of neurotransmitter release, inhibit the binding of both PIns-4,5-P2 and PIns- 3,4,5-P3 to tagmin. Our findings imply that tagmin may operate as a bimodal calcium sensor, switching bound lipids during exocytosis. This connection to polyphosphoinositides, compounds whose levels are physiologically regulated, could be important for long-term memory and learning. |
| Keywords: | conference paper; animals; nerve tissue proteins; calcium; kinetics; recombinant fusion proteins; membrane glycoproteins; molecular recognition; peptide fragments; substrate specificity; binding sites; calcium-binding proteins; liposomes; synaptotagmin; exocytosis; protein lipid interaction; neurotransmitter agents; calcium ion; phosphatidylinositide; neurotransmitter release; micelles; phosphatidylinositols; binding kinetics; synapse vesicle; phosphatidylinositol 4,5 bisphosphate; priority journal; synaptotagmins |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 93 |
| Issue: | 23 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1996-11-12 |
| Start Page: | 13327 |
| End Page: | 13332 |
| Language: | English |
| DOI: | 10.1073/pnas.93.23.13327 |
| PUBMED: | 8917590 |
| PROVIDER: | scopus |
| PMCID: | PMC24092 |
| DOI/URL: | |
| Notes: | Conference Paper -- Export Date: 22 November 2017 -- Source: Scopus |
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