Interactive nanocluster compaction of the ELKS scaffold and Cacophony Ca 2+ channels drives sustained active zone potentiation
- Publication type:
- Journal article
- Metadata:
-
- Abstract
- <jats:p> At presynaptic active zones (AZs), conserved scaffold protein architectures control synaptic vesicle (SV) release by defining the nanoscale distribution and density of voltage-gated Ca <jats:sup>2+</jats:sup> channels (VGCCs). While AZs can potentiate SV release in the minutes range, we lack an understanding of how AZ scaffold components and VGCCs engage into potentiation. We here establish dynamic, intravital single-molecule imaging of endogenously tagged proteins at <jats:italic>Drosophila</jats:italic> AZs undergoing presynaptic homeostatic potentiation. During potentiation, the numbers of α1 VGCC subunit Cacophony (Cac) increased per AZ, while their mobility decreased and nanoscale distribution compacted. These dynamic Cac changes depended on the interaction between Cac channel’s intracellular carboxyl terminus and the membrane-close amino-terminal region of the ELKS-family protein Bruchpilot, whose distribution compacted drastically. The Cac-ELKS/Bruchpilot interaction was also needed for sustained AZ potentiation. Our single-molecule analysis illustrates how the AZ scaffold couples to VGCC nanoscale distribution and dynamics to establish a state of sustained potentiation. </jats:p>
- Autoren
- Tina Ghelani
- Marc Escher
- Ulrich Thomas
- Klara Esch
- Janine Lützkendorf
- Harald Depner
- Marta Maglione
- Pierre Parutto
- Scott Gratz
- Tanja Matkovic-Rachid
- Stefanie Ryglewski
- Alexander M Walter
- David Holcman
- Kate O‘Connor Giles
- Martin Heine
- Stephan J Sigrist
- DOI
- 10.1126/sciadv.ade7804
- eISSN
- 2375-2548
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- Science Advances
- Sprache
- en
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Herausgeber
- American Association for the Advancement of Science (AAAS)
- Herausgeber URL
- http://dx.doi.org/10.1126/sciadv.ade7804
- Datum der Datenerfassung
- 2024
- Titel
- Interactive nanocluster compaction of the ELKS scaffold and Cacophony Ca <sup>2+</sup> channels drives sustained active zone potentiation
- Ausgabe der Zeitschrift
- 9
Data source: Crossref
- Other metadata sources:
-
- Abstract
- At presynaptic active zones (AZs), conserved scaffold protein architectures control synaptic vesicle (SV) release by defining the nanoscale distribution and density of voltage-gated Ca<sup>2+</sup> channels (VGCCs). While AZs can potentiate SV release in the minutes range, we lack an understanding of how AZ scaffold components and VGCCs engage into potentiation. We here establish dynamic, intravital single-molecule imaging of endogenously tagged proteins at <i>Drosophila</i> AZs undergoing presynaptic homeostatic potentiation. During potentiation, the numbers of α1 VGCC subunit Cacophony (Cac) increased per AZ, while their mobility decreased and nanoscale distribution compacted. These dynamic Cac changes depended on the interaction between Cac channel's intracellular carboxyl terminus and the membrane-close amino-terminal region of the ELKS-family protein Bruchpilot, whose distribution compacted drastically. The Cac-ELKS/Bruchpilot interaction was also needed for sustained AZ potentiation. Our single-molecule analysis illustrates how the AZ scaffold couples to VGCC nanoscale distribution and dynamics to establish a state of sustained potentiation.
- Addresses
- Institute for Biology and Genetics, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
- Autoren
- Tina Ghelani
- Marc Escher
- Ulrich Thomas
- Klara Esch
- Janine Lützkendorf
- Harald Depner
- Marta Maglione
- Pierre Parutto
- Scott Gratz
- Tanja Matkovic-Rachid
- Stefanie Ryglewski
- Alexander M Walter
- David Holcman
- Kate O'Connor Giles
- Martin Heine
- Stephan J Sigrist
- DOI
- 10.1126/sciadv.ade7804
- eISSN
- 2375-2548
- Externe Identifier
- PubMed Identifier: 36800417
- PubMed Central ID: PMC9937578
- Funding acknowledgements
- Novo Nordisk Fonden: NNF19OC0056047
- European Research Council: 882673
- Open access
- true
- ISSN
- 2375-2548
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- Science advances
- Schlüsselwörter
- Synapses
- Synaptic Vesicles
- Animals
- Drosophila
- Drosophila Proteins
- Synaptic Transmission
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2023
- Open access status
- Open Access
- Paginierung
- eade7804
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Publisher licence
- CC BY-NC
- Datum der Datenerfassung
- 2023
- Titel
- Interactive nanocluster compaction of the ELKS scaffold and Cacophony Ca<sup>2+</sup> channels drives sustained active zone potentiation.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 9
Files
https://europepmc.org/articles/PMC9937578?pdf=render
Data source: Europe PubMed Central
- Abstract
- At presynaptic active zones (AZs), conserved scaffold protein architectures control synaptic vesicle (SV) release by defining the nanoscale distribution and density of voltage-gated Ca2+ channels (VGCCs). While AZs can potentiate SV release in the minutes range, we lack an understanding of how AZ scaffold components and VGCCs engage into potentiation. We here establish dynamic, intravital single-molecule imaging of endogenously tagged proteins at Drosophila AZs undergoing presynaptic homeostatic potentiation. During potentiation, the numbers of α1 VGCC subunit Cacophony (Cac) increased per AZ, while their mobility decreased and nanoscale distribution compacted. These dynamic Cac changes depended on the interaction between Cac channel's intracellular carboxyl terminus and the membrane-close amino-terminal region of the ELKS-family protein Bruchpilot, whose distribution compacted drastically. The Cac-ELKS/Bruchpilot interaction was also needed for sustained AZ potentiation. Our single-molecule analysis illustrates how the AZ scaffold couples to VGCC nanoscale distribution and dynamics to establish a state of sustained potentiation.
- Autoren
- Tina Ghelani
- Marc Escher
- Ulrich Thomas
- Klara Esch
- Janine Lützkendorf
- Harald Depner
- Marta Maglione
- Pierre Parutto
- Scott Gratz
- Tanja Matkovic-Rachid
- Stefanie Ryglewski
- Alexander M Walter
- David Holcman
- Kate O'Connor Giles
- Martin Heine
- Stephan J Sigrist
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/36800417
- DOI
- 10.1126/sciadv.ade7804
- eISSN
- 2375-2548
- Externe Identifier
- PubMed Central ID: PMC9937578
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- Sci Adv
- Schlüsselwörter
- Animals
- Synapses
- Drosophila
- Synaptic Vesicles
- Drosophila Proteins
- Synaptic Transmission
- Sprache
- eng
- Country
- United States
- Paginierung
- eade7804
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Titel
- Interactive nanocluster compaction of the ELKS scaffold and Cacophony Ca2+ channels drives sustained active zone potentiation.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 9
Data source: PubMed
- Beziehungen:
- Property of