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CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles

Compensatory endocytosis of released synaptic vesicles (SVs) relies on coordinated signaling at the lipid-protein interface. Here, we address the synaptic function of C-terminal binding protein 1 (CtBP1), a ubiquitous regulator of gene expression and membrane trafficking in cultured hippocampal neur...

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Autores principales: Ivanova, Daniela, Imig, Cordelia, Camacho, Marcial, Reinhold, Annika, Guhathakurta, Debarpan, Montenegro-Venegas, Carolina, Cousin, Michael A., Gundelfinger, Eckart D., Rosenmund, Christian, Cooper, Benjamin, Fejtova, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034063/
https://www.ncbi.nlm.nih.gov/pubmed/32075774
http://dx.doi.org/10.1016/j.celrep.2020.01.079
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author Ivanova, Daniela
Imig, Cordelia
Camacho, Marcial
Reinhold, Annika
Guhathakurta, Debarpan
Montenegro-Venegas, Carolina
Cousin, Michael A.
Gundelfinger, Eckart D.
Rosenmund, Christian
Cooper, Benjamin
Fejtova, Anna
author_facet Ivanova, Daniela
Imig, Cordelia
Camacho, Marcial
Reinhold, Annika
Guhathakurta, Debarpan
Montenegro-Venegas, Carolina
Cousin, Michael A.
Gundelfinger, Eckart D.
Rosenmund, Christian
Cooper, Benjamin
Fejtova, Anna
author_sort Ivanova, Daniela
collection PubMed
description Compensatory endocytosis of released synaptic vesicles (SVs) relies on coordinated signaling at the lipid-protein interface. Here, we address the synaptic function of C-terminal binding protein 1 (CtBP1), a ubiquitous regulator of gene expression and membrane trafficking in cultured hippocampal neurons. In the absence of CtBP1, synapses form in greater density and show changes in SV distribution and size. The increased basal neurotransmission and enhanced synaptic depression could be attributed to a higher vesicular release probability and a smaller fraction of release-competent SVs, respectively. Rescue experiments with specifically targeted constructs indicate that, while synaptogenesis and release probability are controlled by nuclear CtBP1, the efficient recycling of SVs relies on its synaptic expression. The ability of presynaptic CtBP1 to facilitate compensatory endocytosis depends on its membrane-fission activity and the activation of the lipid-metabolizing enzyme PLD1. Thus, CtBP1 regulates SV recycling by promoting a permissive lipid environment for compensatory endocytosis.
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spelling pubmed-70340632020-02-27 CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles Ivanova, Daniela Imig, Cordelia Camacho, Marcial Reinhold, Annika Guhathakurta, Debarpan Montenegro-Venegas, Carolina Cousin, Michael A. Gundelfinger, Eckart D. Rosenmund, Christian Cooper, Benjamin Fejtova, Anna Cell Rep Article Compensatory endocytosis of released synaptic vesicles (SVs) relies on coordinated signaling at the lipid-protein interface. Here, we address the synaptic function of C-terminal binding protein 1 (CtBP1), a ubiquitous regulator of gene expression and membrane trafficking in cultured hippocampal neurons. In the absence of CtBP1, synapses form in greater density and show changes in SV distribution and size. The increased basal neurotransmission and enhanced synaptic depression could be attributed to a higher vesicular release probability and a smaller fraction of release-competent SVs, respectively. Rescue experiments with specifically targeted constructs indicate that, while synaptogenesis and release probability are controlled by nuclear CtBP1, the efficient recycling of SVs relies on its synaptic expression. The ability of presynaptic CtBP1 to facilitate compensatory endocytosis depends on its membrane-fission activity and the activation of the lipid-metabolizing enzyme PLD1. Thus, CtBP1 regulates SV recycling by promoting a permissive lipid environment for compensatory endocytosis. Cell Press 2020-02-18 /pmc/articles/PMC7034063/ /pubmed/32075774 http://dx.doi.org/10.1016/j.celrep.2020.01.079 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ivanova, Daniela
Imig, Cordelia
Camacho, Marcial
Reinhold, Annika
Guhathakurta, Debarpan
Montenegro-Venegas, Carolina
Cousin, Michael A.
Gundelfinger, Eckart D.
Rosenmund, Christian
Cooper, Benjamin
Fejtova, Anna
CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles
title CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles
title_full CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles
title_fullStr CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles
title_full_unstemmed CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles
title_short CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles
title_sort ctbp1-mediated membrane fission contributes to effective recycling of synaptic vesicles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034063/
https://www.ncbi.nlm.nih.gov/pubmed/32075774
http://dx.doi.org/10.1016/j.celrep.2020.01.079
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