Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with Munc18.
Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic information is limited. Acid sphingomyelinase knockout mice (ASMko) are a suitable model to address the role of sphingolipids in synaptic regulation as they recapitulate a mental retardation syndrome, N...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005310&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850108048384720896 |
|---|---|
| author | Paola G Camoletto Hugo Vara Laura Morando Emma Connell Fabio P Marletto Maurizio Giustetto Marco Sassoè-Pognetto Paul P Van Veldhoven Maria Dolores Ledesma |
| author_facet | Paola G Camoletto Hugo Vara Laura Morando Emma Connell Fabio P Marletto Maurizio Giustetto Marco Sassoè-Pognetto Paul P Van Veldhoven Maria Dolores Ledesma |
| author_sort | Paola G Camoletto |
| collection | DOAJ |
| description | Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic information is limited. Acid sphingomyelinase knockout mice (ASMko) are a suitable model to address the role of sphingolipids in synaptic regulation as they recapitulate a mental retardation syndrome, Niemann Pick disease type A (NPA), and their neurons have altered levels of sphingomyelin (SM) and its derivatives. Electrophysiological recordings showed that ASMko hippocampi have increased paired-pulse facilitation and post-tetanic potentiation. Consistently, electron microscopy revealed reduced number of docked vesicles. Biochemical analysis of ASMko synaptic membranes unveiled higher amounts of SM and sphingosine (Se) and enhanced interaction of the docking molecules Munc18 and syntaxin1. In vitro reconstitution assays demonstrated that Se changes syntaxin1 conformation enhancing its interaction with Munc18. Moreover, Se reduces vesicle docking in primary neurons and increases paired-pulse facilitation when added to wt hippocampal slices. These data provide with a novel mechanism for synaptic vesicle control by sphingolipids and could explain cognitive deficits of NPA patients. |
| format | Article |
| id | doaj-art-ea6987fcec6c419ea64acb42c9c2419a |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-ea6987fcec6c419ea64acb42c9c2419a2025-08-20T02:38:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0144e531010.1371/journal.pone.0005310Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with Munc18.Paola G CamolettoHugo VaraLaura MorandoEmma ConnellFabio P MarlettoMaurizio GiustettoMarco Sassoè-PognettoPaul P Van VeldhovenMaria Dolores LedesmaConsensus exists that lipids must play key functions in synaptic activity but precise mechanistic information is limited. Acid sphingomyelinase knockout mice (ASMko) are a suitable model to address the role of sphingolipids in synaptic regulation as they recapitulate a mental retardation syndrome, Niemann Pick disease type A (NPA), and their neurons have altered levels of sphingomyelin (SM) and its derivatives. Electrophysiological recordings showed that ASMko hippocampi have increased paired-pulse facilitation and post-tetanic potentiation. Consistently, electron microscopy revealed reduced number of docked vesicles. Biochemical analysis of ASMko synaptic membranes unveiled higher amounts of SM and sphingosine (Se) and enhanced interaction of the docking molecules Munc18 and syntaxin1. In vitro reconstitution assays demonstrated that Se changes syntaxin1 conformation enhancing its interaction with Munc18. Moreover, Se reduces vesicle docking in primary neurons and increases paired-pulse facilitation when added to wt hippocampal slices. These data provide with a novel mechanism for synaptic vesicle control by sphingolipids and could explain cognitive deficits of NPA patients.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005310&type=printable |
| spellingShingle | Paola G Camoletto Hugo Vara Laura Morando Emma Connell Fabio P Marletto Maurizio Giustetto Marco Sassoè-Pognetto Paul P Van Veldhoven Maria Dolores Ledesma Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with Munc18. PLoS ONE |
| title | Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with Munc18. |
| title_full | Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with Munc18. |
| title_fullStr | Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with Munc18. |
| title_full_unstemmed | Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with Munc18. |
| title_short | Synaptic vesicle docking: sphingosine regulates syntaxin1 interaction with Munc18. |
| title_sort | synaptic vesicle docking sphingosine regulates syntaxin1 interaction with munc18 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005310&type=printable |
| work_keys_str_mv | AT paolagcamoletto synapticvesicledockingsphingosineregulatessyntaxin1interactionwithmunc18 AT hugovara synapticvesicledockingsphingosineregulatessyntaxin1interactionwithmunc18 AT lauramorando synapticvesicledockingsphingosineregulatessyntaxin1interactionwithmunc18 AT emmaconnell synapticvesicledockingsphingosineregulatessyntaxin1interactionwithmunc18 AT fabiopmarletto synapticvesicledockingsphingosineregulatessyntaxin1interactionwithmunc18 AT mauriziogiustetto synapticvesicledockingsphingosineregulatessyntaxin1interactionwithmunc18 AT marcosassoepognetto synapticvesicledockingsphingosineregulatessyntaxin1interactionwithmunc18 AT paulpvanveldhoven synapticvesicledockingsphingosineregulatessyntaxin1interactionwithmunc18 AT mariadoloresledesma synapticvesicledockingsphingosineregulatessyntaxin1interactionwithmunc18 |