DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Tae Sun | ko |
dc.contributor.author | Lee, Joo-Young | ko |
dc.contributor.author | Kyung, Jae Won | ko |
dc.contributor.author | Yang, Yoosoo | ko |
dc.contributor.author | Park, Seung Ju | ko |
dc.contributor.author | Lee, Seulgi | ko |
dc.contributor.author | Pavlovic , Igor | ko |
dc.contributor.author | Kong, Byoungjae | ko |
dc.contributor.author | Jho, Yong Seok | ko |
dc.contributor.author | Jessen, Henning J | ko |
dc.contributor.author | Kweon, Dae Hyuk | ko |
dc.contributor.author | Shin, Yeon Kyun | ko |
dc.contributor.author | Kim, Sung Hyun | ko |
dc.contributor.author | Yoon, Tae Young | ko |
dc.contributor.author | Kim, Seyun | ko |
dc.date.accessioned | 2016-09-08T00:50:07Z | - |
dc.date.available | 2016-09-08T00:50:07Z | - |
dc.date.created | 2016-07-23 | - |
dc.date.created | 2016-07-23 | - |
dc.date.issued | 2016-07 | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.113, no.29, pp.8314 - 8319 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10203/212921 | - |
dc.description.abstract | Inositol pyrophosphates such as 5-diphosphoinositol pentakisphosphate (5-IP7) are highly energetic inositol metabolites containing phosphoanhydride bonds. Although inositol pyrophosphates are known to regulate various biological events, including growth, survival, and metabolism, the molecular sites of 5-IP7 action in vesicle trafficking have remained largely elusive. We report here that elevated 5-IP7 levels, caused by overexpression of inositol hexakisphosphate (IP6) kinase 1 (IP6K1), suppressed depolarization-induced neurotransmitter release from PC12 cells. Conversely, IP6K1 depletion decreased intracellular 5-IP7 concentrations, leading to increased neurotransmitter release. Consistently, knockdown of IP6K1 in cultured hippocampal neurons augmented action potential-driven synaptic vesicle exocytosis at synapses. Using a FRET-based in vitro vesicle fusion assay, we found that 5-IP7, but not 1-IP7, exhibited significantly higher inhibitory activity toward synaptic vesicle exocytosis than IP6. Synaptotagmin 1 (Syt1), a Ca2+ sensor essential for synaptic membrane fusion, was identified as a molecular target of 5-IP7. Notably, 5-IP7 showed a 45-fold higher binding affinity for Syt1 compared with IP6. In addition, 5-IP7-dependent inhibition of synaptic vesicle fusion was abolished by increasing Ca2+ levels. Thus, 5-IP7 appears to act through Syt1 binding to interfere with the fusogenic activity of Ca2+. These findings reveal a role of 5-IP7 as a potent inhibitor of Syt1 in controlling the synaptic exocytotic pathway and expand our understanding of the signaling mechanisms of inositol pyrophosphates. | - |
dc.language | English | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.subject | SQUID GIANT SYNAPSE | - |
dc.subject | MEMBRANE-FUSION | - |
dc.subject | C2B DOMAIN | - |
dc.subject | NEUROTRANSMITTER RELEASE | - |
dc.subject | DIPHOSPHOINOSITOL POLYPHOSPHATES | - |
dc.subject | NERVE-TERMINALS | - |
dc.subject | VESICLE FUSION | - |
dc.subject | HEXAKISPHOSPHATE | - |
dc.subject | CELLS | - |
dc.subject | TRANSMISSION | - |
dc.title | Inositol pyrophosphates inhibit synaptotagmin-dependent exocytosis | - |
dc.type | Article | - |
dc.identifier.wosid | 000380224500084 | - |
dc.identifier.scopusid | 2-s2.0-84978870616 | - |
dc.type.rims | ART | - |
dc.citation.volume | 113 | - |
dc.citation.issue | 29 | - |
dc.citation.beginningpage | 8314 | - |
dc.citation.endingpage | 8319 | - |
dc.citation.publicationname | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.identifier.doi | 10.1073/pnas.1521600113 | - |
dc.contributor.localauthor | Kim, Seyun | - |
dc.contributor.nonIdAuthor | Lee, Joo-Young | - |
dc.contributor.nonIdAuthor | Kyung, Jae Won | - |
dc.contributor.nonIdAuthor | Yang, Yoosoo | - |
dc.contributor.nonIdAuthor | Pavlovic , Igor | - |
dc.contributor.nonIdAuthor | Kong, Byoungjae | - |
dc.contributor.nonIdAuthor | Jho, Yong Seok | - |
dc.contributor.nonIdAuthor | Jessen, Henning J | - |
dc.contributor.nonIdAuthor | Kweon, Dae Hyuk | - |
dc.contributor.nonIdAuthor | Shin, Yeon Kyun | - |
dc.contributor.nonIdAuthor | Kim, Sung Hyun | - |
dc.contributor.nonIdAuthor | Yoon, Tae Young | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | inositol pyrophosphate | - |
dc.subject.keywordAuthor | synaptotagmin | - |
dc.subject.keywordAuthor | synaptic vesicle exocytosis | - |
dc.subject.keywordPlus | SQUID GIANT SYNAPSE | - |
dc.subject.keywordPlus | MEMBRANE-FUSION | - |
dc.subject.keywordPlus | C2B DOMAIN | - |
dc.subject.keywordPlus | NEUROTRANSMITTER RELEASE | - |
dc.subject.keywordPlus | DIPHOSPHOINOSITOL POLYPHOSPHATES | - |
dc.subject.keywordPlus | NERVE-TERMINALS | - |
dc.subject.keywordPlus | VESICLE FUSION | - |
dc.subject.keywordPlus | HEXAKISPHOSPHATE | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | TRANSMISSION | - |
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